{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T15:02:30Z","timestamp":1789743750949,"version":"4.0.1"},"reference-count":87,"publisher":"Rockefeller University Press","issue":"10","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/rupress.org\/pages\/terms102024"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["SNF310030_156517"],"award-info":[{"award-number":["SNF310030_156517"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["PR00P3_193084"],"award-info":[{"award-number":["PR00P3_193084"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["310030_212312"],"award-info":[{"award-number":["310030_212312"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Monash Platform Access","award":["PAG19-0569"],"award-info":[{"award-number":["PAG19-0569"]}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["FOR2599"],"award-info":[{"award-number":["FOR2599"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["ES 471\/3-2"],"award-info":[{"award-number":["ES 471\/3-2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["SPP2306"],"award-info":[{"award-number":["SPP2306"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["ES 471\/6-1"],"award-info":[{"award-number":["ES 471\/6-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,10,5]]},"abstract":"<jats:p>Macrophage polarization by type-2 cytokines is central to anti-helminth immunity and tissue repair. While some hallmark changes in macrophages are well-characterized and associated with protection against helminths, it is still unclear how macrophages exert their anti-helminth effects. In this context, we investigated arachidonate 15-lipoxygenase (LOX) (Alox15), a LOX well known for its role in macrophage polarization in the context of metabolic diseases, and a hallmark of type-2 macrophage (M2) human polarization. We show that in the absence of Alox15, M2 cannot trap and kill helminths. Surprisingly, expression of M2 markers was normal despite a loss of function. Instead, we found a concomitant increase in pro-inflammatory responses due to an uncontrolled activation of glycolysis. We further show that activation of Peroxisome proliferator-activated receptor-delta (PPAR-\u03b4) by lipids downstream of docosapentaenoic acid (DPA) can restore normal glycolysis control, highlighting a novel role of lipids in the fine-tuning of the metabolic support required for optimal macrophage polarization.<\/jats:p>","DOI":"10.1084\/jem.20241620","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:20:56Z","timestamp":1787034056000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Alox15 restrains glycolysis to support M2 macrophage effector function during helminth immunity"],"prefix":"10.1084","volume":"223","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4536-9826","authenticated-orcid":true,"given":"Dovran","family":"Ovezgeldiyev","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03adhka07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Swiss Tropical and Public Health Institute 2 Helminth Immunology, , Allschwill,","place":["Switzerland"]},{"id":[{"id":"https:\/\/ror.org\/02s6k3f65","id-type":"ROR","asserted-by":"publisher"}],"name":"Basel University 3 , Basel,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5900-9186","authenticated-orcid":true,"given":"Vanessa","family":"Trefzer","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03adhka07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Swiss Tropical and Public Health Institute 2 Helminth Immunology, , Allschwill,","place":["Switzerland"]},{"id":[{"id":"https:\/\/ror.org\/02s6k3f65","id-type":"ROR","asserted-by":"publisher"}],"name":"Basel University 3 , Basel,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9592-7607","authenticated-orcid":true,"given":"Rory","family":"Doolan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bfwt286","id-type":"ROR","asserted-by":"publisher"}],"name":"Monash University 1 Laboratory of Intestinal Immunology, Department of Immunology and Pathology, , Melbourne,","place":["Australia"]},{"id":[{"id":"https:\/\/ror.org\/03adhka07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Swiss Tropical and Public Health Institute 2 Helminth Immunology, , Allschwill,","place":["Switzerland"]},{"id":[{"id":"https:\/\/ror.org\/02s6k3f65","id-type":"ROR","asserted-by":"publisher"}],"name":"Basel University 3 , Basel,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9233-5320","authenticated-orcid":true,"given":"Mati","family":"Moyat","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bfwt286","id-type":"ROR","asserted-by":"publisher"}],"name":"Monash University 1 Laboratory of Intestinal Immunology, Department of Immunology and Pathology, , Melbourne,","place":["Australia"]},{"id":[{"id":"https:\/\/ror.org\/02s376052","id-type":"ROR","asserted-by":"publisher"}],"name":"Global Health Institute, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL) 4 , Lausanne,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4628-7890","authenticated-orcid":true,"given":"Gillian","family":"Coakley","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bfwt286","id-type":"ROR","asserted-by":"publisher"}],"name":"Monash University 1 Laboratory of Intestinal Immunology, Department of Immunology and Pathology, , Melbourne,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8733-2945","authenticated-orcid":true,"given":"Lakshanie C.","family":"Wickramasinghe","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bfwt286","id-type":"ROR","asserted-by":"publisher"}],"name":"Monash University 1 Laboratory of Intestinal Immunology, Department of Immunology and Pathology, , Melbourne,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3890-9699","authenticated-orcid":true,"given":"Carmel","family":"Daunt","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bfwt286","id-type":"ROR","asserted-by":"publisher"}],"name":"Monash University 1 Laboratory of Intestinal Immunology, Department of Immunology and Pathology, , Melbourne,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8423-5584","authenticated-orcid":true,"given":"Beatrice","family":"Volpe","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02s376052","id-type":"ROR","asserted-by":"publisher"}],"name":"Global Health Institute, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL) 4 , Lausanne,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3198-2046","authenticated-orcid":true,"given":"Fiona","family":"Henkel","sequence":"additional","affiliation":[{"name":"Center of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich 5 , Munich,","place":["Germany"]},{"id":[{"id":"https:\/\/ror.org\/019whta54","id-type":"ROR","asserted-by":"publisher"}],"name":"Universit\u00e9 de Lausanne 6 Department of Immunobiology, , Epalinges,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2093-8502","authenticated-orcid":true,"given":"Alex","family":"Serra","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03adhka07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Swiss Tropical and Public Health Institute 2 Helminth Immunology, , Allschwill,","place":["Switzerland"]},{"id":[{"id":"https:\/\/ror.org\/02s6k3f65","id-type":"ROR","asserted-by":"publisher"}],"name":"Basel University 3 , Basel,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6673-8382","authenticated-orcid":true,"given":"Maike","family":"Hartmann","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03adhka07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Swiss Tropical and Public Health Institute 2 Helminth Immunology, , Allschwill,","place":["Switzerland"]},{"id":[{"id":"https:\/\/ror.org\/02s6k3f65","id-type":"ROR","asserted-by":"publisher"}],"name":"Basel University 3 , Basel,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8097-1790","authenticated-orcid":true,"given":"Shirin","family":"Rezaei","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03adhka07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Swiss Tropical and Public Health Institute 2 Helminth Immunology, , Allschwill,","place":["Switzerland"]},{"id":[{"id":"https:\/\/ror.org\/02s6k3f65","id-type":"ROR","asserted-by":"publisher"}],"name":"Basel University 3 , Basel,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0177-4134","authenticated-orcid":true,"given":"Niki","family":"Ubags","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/019whta54","id-type":"ROR","asserted-by":"publisher"}],"name":"Service de Pneumologie, CHUV, University of Lausanne 7 Faculty of Biology and Medicine, , Epalinges,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2122-2975","authenticated-orcid":true,"given":"Alana","family":"Butler","sequence":"additional","affiliation":[{"name":"School of Translational Medicine Monash University 8 Department of Immunology, , Melbourne,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8387-0881","authenticated-orcid":true,"given":"Roxanne","family":"Chatzis","sequence":"additional","affiliation":[{"name":"School of Translational Medicine Monash University 8 Department of Immunology, , Melbourne,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1457-3160","authenticated-orcid":true,"given":"Benjamin J.","family":"Marsland","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/019whta54","id-type":"ROR","asserted-by":"publisher"}],"name":"Service de Pneumologie, CHUV, University of Lausanne 7 Faculty of Biology and Medicine, , Epalinges,","place":["Switzerland"]},{"name":"School of Translational Medicine Monash University 8 Department of Immunology, , Melbourne,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4593-3042","authenticated-orcid":true,"given":"Adam Alexander T.","family":"Smith","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01bmjkv45","id-type":"ROR","asserted-by":"publisher"}],"name":"Friedrich Miescher Institute for Biomedical Research (FMI) 9 , Basel,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6457-3823","authenticated-orcid":true,"given":"Deanna","family":"Deveson Lucas","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bfwt286","id-type":"ROR","asserted-by":"publisher"}],"name":"Monash Bioinformatic Platform, Monash University 10 , Melbourne,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7517-2147","authenticated-orcid":true,"given":"Erin N.S.","family":"McGowan","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute 11 , Parkville,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1139-3308","authenticated-orcid":true,"given":"Kathrina J.","family":"Binger","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01rxfrp27","id-type":"ROR","asserted-by":"publisher"}],"name":"La Trobe Institute for Molecular Science, La Trobe University 12 Department of Biochemistry and Chemistry, , Bundoora,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7107-7887","authenticated-orcid":true,"given":"Malcolm J.","family":"McConville","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01rxfrp27","id-type":"ROR","asserted-by":"publisher"}],"name":"La Trobe Institute for Molecular Science, La Trobe University 12 Department of Biochemistry and Chemistry, , Bundoora,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1898-9382","authenticated-orcid":true,"given":"Julia","family":"Esser-von Bieren","sequence":"additional","affiliation":[{"name":"Center of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich 5 , Munich,","place":["Germany"]},{"id":[{"id":"https:\/\/ror.org\/019whta54","id-type":"ROR","asserted-by":"publisher"}],"name":"Universit\u00e9 de Lausanne 6 Department of Immunobiology, , Epalinges,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2922-0210","authenticated-orcid":true,"given":"Nicola L.","family":"Harris","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bfwt286","id-type":"ROR","asserted-by":"publisher"}],"name":"Monash University 1 Laboratory of Intestinal Immunology, Department of Immunology and Pathology, , Melbourne,","place":["Australia"]},{"id":[{"id":"https:\/\/ror.org\/02s376052","id-type":"ROR","asserted-by":"publisher"}],"name":"Global Health Institute, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL) 4 , Lausanne,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3743-7356","authenticated-orcid":true,"given":"Tiffany","family":"Bouchery","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bfwt286","id-type":"ROR","asserted-by":"publisher"}],"name":"Monash University 1 Laboratory of Intestinal Immunology, Department of Immunology and Pathology, , Melbourne,","place":["Australia"]},{"id":[{"id":"https:\/\/ror.org\/03adhka07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Swiss Tropical and Public Health Institute 2 Helminth Immunology, , Allschwill,","place":["Switzerland"]},{"id":[{"id":"https:\/\/ror.org\/02s6k3f65","id-type":"ROR","asserted-by":"publisher"}],"name":"Basel University 3 , Basel,","place":["Switzerland"]},{"id":[{"id":"https:\/\/ror.org\/02s376052","id-type":"ROR","asserted-by":"publisher"}],"name":"Global Health Institute, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL) 4 , Lausanne,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"2026091810035709500_bib1","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/j.bbalip.2016.07.014","article-title":"The double-edged role of 12\/15-lipoxygenase during inflammation and immunity","volume":"1862","author":"Ackermann","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"2026091810035709500_bib2","doi-asserted-by":"publisher","first-page":"1564","DOI":"10.1016\/j.immuni.2022.08.010","article-title":"Biology of lung macrophages in health and disease","volume":"55","author":"Aegerter","year":"2022","journal-title":"Immunity"},{"key":"2026091810035709500_bib3","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adn2717","article-title":"PPAR\u03b2\/\u03b4-orchestrated metabolic reprogramming supports the formation and maintenance of memory CD8+ T cells","volume":"9","author":"Bevilacqua","year":"2024","journal-title":"Sci. Immunol."},{"key":"2026091810035709500_bib4","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1172\/JCI5241","article-title":"Resistance to type 1 diabetes induction in 12-lipoxygenase knockout mice","volume":"103","author":"Bleich","year":"1999","journal-title":"J. Clin. Invest."},{"key":"2026091810035709500_bib5","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1126\/science.aai8132","article-title":"Macrophage function in tissue repair and remodeling requires IL-4 or IL-13 with apoptotic cells","volume":"356","author":"Bosurgi","year":"2017","journal-title":"Science"},{"key":"2026091810035709500_bib6","doi-asserted-by":"publisher","first-page":"6970","DOI":"10.1038\/ncomms7970","article-title":"ILC2s and T cells cooperate to ensure maintenance of M2 macrophages for lung immunity against hookworms","volume":"6","author":"Bouchery","year":"2015","journal-title":"Nat. Commun."},{"key":"2026091810035709500_bib7","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1111\/imcb.12536","article-title":"\u03b2-Glucan receptors on IL-4 activated macrophages are required for hookworm larvae recognition and trapping","volume":"100","author":"Bouchery","year":"2022","journal-title":"Immunol. Cell Biol."},{"key":"2026091810035709500_bib8","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1002\/cpmo.34","article-title":"The study of host immune responses elicited by the model murine hookworms Nippostrongylus brasiliensis and Heligmosomoides polygyrus","volume":"7","author":"Bouchery","year":"2017","journal-title":"Curr. Protoc. Mouse Biol."},{"key":"2026091810035709500_bib87","doi-asserted-by":"publisher","first-page":"Unit 19.12","DOI":"10.1002\/0471142735.im1912s55","article-title":"Animal model of Nippostrongylus brasiliensis and Heligmosomoides polygyrus.","volume":"Chapter 19","author":"Camberis","year":"2003","journal-title":"Curr. Protoc. Immunol."},{"key":"2026091810035709500_bib9","doi-asserted-by":"publisher","first-page":"110215","DOI":"10.1016\/j.celrep.2021.110215","article-title":"Helminth resistance is mediated by differential activation of recruited monocyte-derived alveolar macrophages and arginine depletion","volume":"38","author":"Chen","year":"2022","journal-title":"Cell Rep"},{"key":"2026091810035709500_bib10","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1038\/nm.2628","article-title":"An essential role for TH2-type responses in limiting acute tissue damage during experimental helminth infection","volume":"18","author":"Chen","year":"2012","journal-title":"Nat. Med."},{"key":"2026091810035709500_bib11","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1038\/ni.2984","article-title":"Neutrophils prime a long-lived effector macrophage phenotype that mediates accelerated helminth expulsion","volume":"15","author":"Chen","year":"2014","journal-title":"Nat. Immunol."},{"key":"2026091810035709500_bib12","doi-asserted-by":"publisher","DOI":"10.1111\/pim.12717","article-title":"Interactions between macrophages and helminths","volume":"42","author":"Coakley","year":"2020","journal-title":"Parasite Immunol."},{"key":"2026091810035709500_bib13","doi-asserted-by":"publisher","first-page":"11423","DOI":"10.1038\/s41598-020-68347-x","article-title":"PPARbeta\/delta-dependent MSC metabolism determines their immunoregulatory properties","volume":"10","author":"Contreras-Lopez","year":"2020","journal-title":"Sci. Rep."},{"key":"2026091810035709500_bib14","doi-asserted-by":"publisher","first-page":"2277","DOI":"10.1161\/01.cir.103.18.2277","article-title":"Absence of 12\/15-lipoxygenase expression decreases lipid peroxidation and atherogenesis in apolipoprotein e-deficient mice","volume":"103","author":"Cyrus","year":"2001","journal-title":"Circulation"},{"key":"2026091810035709500_bib15","doi-asserted-by":"publisher","first-page":"1597","DOI":"10.1172\/JCI5897","article-title":"Disruption of the 12\/15-lipoxygenase gene diminishes atherosclerosis in apo E-deficient mice","volume":"103","author":"Cyrus","year":"1999","journal-title":"J. Clin. Invest."},{"key":"2026091810035709500_bib16","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1016\/j.imbio.2012.08.270","article-title":"Identification of novel markers of alternative activation and potential endogenous PPARgamma ligand production mechanisms in human IL-4 stimulated differentiating macrophages","volume":"217","author":"Czimmerer","year":"2012","journal-title":"Immunobiology"},{"key":"2026091810035709500_bib17","doi-asserted-by":"publisher","first-page":"112471","DOI":"10.1016\/j.celrep.2023.112471","article-title":"The glycolysis\/HIF-1alpha axis defines the inflammatory role of IL-4-primed macrophages","volume":"42","author":"Dang","year":"2023","journal-title":"Cell Rep."},{"key":"2026091810035709500_bib18","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aay0605","article-title":"An anti-inflammatory eicosanoid switch mediates the suppression of type-2 inflammation by helminth larval products","volume":"12","author":"de Los Reyes Jim\u00e9nez","year":"2020","journal-title":"Sci. Transl Med."},{"key":"2026091810035709500_bib19","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaw3703","article-title":"Helminth infections drive heterogeneity in human type 2 and regulatory cells","volume":"12","author":"de Ruiter","year":"2020","journal-title":"Sci. Transl Med."},{"key":"2026091810035709500_bib20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0119751","article-title":"Transcriptomic analysis of human polarized macrophages: More than one role of alternative activation?","volume":"10","author":"Derlindati","year":"2015","journal-title":"PLoS One"},{"key":"2026091810035709500_bib21","doi-asserted-by":"publisher","first-page":"3319","DOI":"10.1002\/eji.200737765","article-title":"Mapping immune response profiles: The emerging scenario from helminth immunology","volume":"37","author":"D\u00edaz","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"2026091810035709500_bib22","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1016\/j.pt.2018.07.005","article-title":"Lessons along the critical path: Developing vaccines against human helminths","volume":"34","author":"Diemert","year":"2018","journal-title":"Trends Parasitol."},{"key":"2026091810035709500_bib23","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"2026091810035709500_bib24","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1136\/thoraxjnl-2015-207035","article-title":"\u2018LungGENS\u2019: A web-based tool for mapping single-cell gene expression in the developing lung","volume":"70","author":"Du","year":"2015","journal-title":"Thorax"},{"key":"2026091810035709500_bib25","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1136\/thoraxjnl-2016-209598","article-title":"Lung gene expression analysis (LGEA): An integrative web portal for comprehensive gene expression data analysis in lung development","volume":"72","author":"Du","year":"2017","journal-title":"Thorax"},{"key":"2026091810035709500_bib26","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1165\/rcmb.2020-0308LE","article-title":"Lung gene expression analysis web portal version 3: Lung-at-a-Glance","volume":"64","author":"Du","year":"2021","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2026091810035709500_bib27","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1016\/j.chom.2017.09.006","article-title":"Epithelial-cell-derived Phospholipase A2 group 1B is an endogenous anthelmintic","volume":"22","author":"Entwistle","year":"2017","journal-title":"Cell Host Microbe"},{"key":"2026091810035709500_bib28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003771","article-title":"Antibodies trap tissue migrating helminth larvae and prevent tissue damage by driving IL-4Ralpha-independent alternative differentiation of macrophages","volume":"9","author":"Esser-von Bieren","year":"2013","journal-title":"PLoS Pathog."},{"key":"2026091810035709500_bib29","doi-asserted-by":"publisher","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","article-title":"MultiQC: Summarize analysis results for multiple tools and samples in a single report","volume":"32","author":"Ewels","year":"2016","journal-title":"Bioinformatics"},{"key":"2026091810035709500_bib30","doi-asserted-by":"publisher","first-page":"2531","DOI":"10.1016\/j.immuni.2021.09.010","article-title":"IL-33-induced metabolic reprogramming controls the differentiation of alternatively activated macrophages and the resolution of inflammation","volume":"54","author":"Faas","year":"2021","journal-title":"Immunity"},{"key":"2026091810035709500_bib31","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1016\/j.immuni.2023.02.016","article-title":"T helper 2 cells control monocyte to tissue-resident macrophage differentiation during nematode infection of the pleural cavity","volume":"56","author":"Finlay","year":"2023","journal-title":"Immunity"},{"key":"2026091810035709500_bib32","doi-asserted-by":"publisher","first-page":"D766","DOI":"10.1093\/nar\/gky955","article-title":"GENCODE reference annotation for the human and mouse genomes","volume":"47","author":"Frankish","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2026091810035709500_bib33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005494","article-title":"An arginine deprivation response pathway is induced in Leishmania during macrophage invasion","volume":"12","author":"Goldman-Pinkovich","year":"2016","journal-title":"PLoS Pathog."},{"key":"2026091810035709500_bib34","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s12915-017-0392-4","article-title":"Tissue macrophages: Heterogeneity and functions","volume":"15","author":"Gordon","year":"2017","journal-title":"BMC Biol."},{"key":"2026091810035709500_bib35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056763","article-title":"Deletion of 12\/15-lipoxygenase alters macrophage and islet function in NOD-Alox15(null) mice, leading to protection against type 1 diabetes development","volume":"8","author":"Green-Mitchell","year":"2013","journal-title":"PLoS One"},{"key":"2026091810035709500_bib36","doi-asserted-by":"publisher","first-page":"e110","DOI":"10.1182\/blood-2013-08-520619","article-title":"Alternatively activated macrophages derived from monocytes and tissue macrophages are phenotypically and functionally distinct","volume":"123","author":"Gundra","year":"2014","journal-title":"Blood"},{"key":"2026091810035709500_bib37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085085","article-title":"Interleukin-4-mediated 15-lipoxygenase-1 trans-activation requires UTX recruitment and H3K27me3 demethylation at the promoter in A549 cells","volume":"9","author":"Han","year":"2014","journal-title":"PLoS One"},{"key":"2026091810035709500_bib38","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","article-title":"Dictionary learning for integrative, multimodal and scalable single-cell analysis","volume":"42","author":"Hao","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"2026091810035709500_bib39","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1111\/all.13700","article-title":"House dust mite drives proinflammatory eicosanoid reprogramming and macrophage effector functions","volume":"74","author":"Henkel","year":"2019","journal-title":"Allergy"},{"key":"2026091810035709500_bib40","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.193","article-title":"Single-cell transcriptomics reveals distinct cell response between acute and chronic pulmonary infection of Pseudomonas aeruginosa","volume":"3","author":"Hu","year":"2022","journal-title":"MedComm (2020)"},{"key":"2026091810035709500_bib41","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1038\/22572","article-title":"Interleukin-4-dependent production of PPAR-gamma ligands in macrophages by 12\/15-lipoxygenase","volume":"400","author":"Huang","year":"1999","journal-title":"Nature"},{"key":"2026091810035709500_bib42","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1016\/j.immuni.2016.09.016","article-title":"Metabolic reprogramming mediated by the mTORC2-IRF4 signaling Axis is essential for macrophage alternative activation","volume":"45","author":"Huang","year":"2016","journal-title":"Immunity"},{"key":"2026091810035709500_bib43","doi-asserted-by":"publisher","first-page":"3694","DOI":"10.1111\/febs.15715","article-title":"More than just protein building blocks: How amino acids and related metabolic pathways fuel macrophage polarization","volume":"288","author":"Kieler","year":"2021","journal-title":"FEBS J."},{"key":"2026091810035709500_bib44","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1042\/0264-6021:3630157","article-title":"Nuclear receptor corepressor-dependent repression of peroxisome-proliferator-activated receptor delta-mediated transactivation","volume":"363","author":"Krogsdam","year":"2002","journal-title":"Biochem. J."},{"key":"2026091810035709500_bib45","doi-asserted-by":"publisher","first-page":"101526","DOI":"10.1016\/j.smim.2021.101526","article-title":"Macrophage regulation & function in helminth infection","volume":"53","author":"Lechner","year":"2021","journal-title":"Semin. Immunol."},{"key":"2026091810035709500_bib46","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: an efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"2026091810035709500_bib47","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1038\/s41385-022-00532-9","article-title":"Effects of helminths on the human immune response and the microbiome","volume":"15","author":"Loke","year":"2022","journal-title":"Mucosal Immunol."},{"key":"2026091810035709500_bib48","doi-asserted-by":"publisher","first-page":"3140","DOI":"10.1038\/s41418-021-00807-x","article-title":"Loss of 15-lipoxygenase disrupts T(reg) differentiation altering their pro-resolving functions","volume":"28","author":"Marques","year":"2021","journal-title":"Cell Death Differ"},{"key":"2026091810035709500_bib49","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1158\/0008-5472.CAN-17-0908","article-title":"PPAR\u03b4 elicits ligand-independent repression of trefoil factor family to limit prostate cancer growth","volume":"78","author":"Mart\u00edn-Mart\u00edn","year":"2018","journal-title":"Cancer Res."},{"key":"2026091810035709500_bib50","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1093\/bioinformatics\/btw777","article-title":"Scater: Pre-processing, quality control, normalization and visualization of single-cell RNA-seq data in R","volume":"33","author":"McCarthy","year":"2017","journal-title":"Bioinformatics"},{"key":"2026091810035709500_bib51","doi-asserted-by":"publisher","first-page":"104520","DOI":"10.1016\/j.isci.2022.104520","article-title":"Tetraspanin CD82 restrains phagocyte migration but supports macrophage activation","volume":"25","author":"McGowan","year":"2022","journal-title":"iScience"},{"key":"2026091810035709500_bib52","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1126\/science.aaj2067","article-title":"Local amplifiers of IL-4R\u03b1-mediated macrophage activation promote repair in lung and liver","volume":"356","author":"Minutti","year":"2017","journal-title":"Science"},{"key":"2026091810035709500_bib53","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1038\/s41385-022-00498-8","article-title":"Microbial regulation of intestinal motility provides resistance against helminth infection","volume":"15","author":"Moyat","year":"2022","journal-title":"Mucosal Immunol."},{"key":"2026091810035709500_bib54","doi-asserted-by":"publisher","first-page":"2682","DOI":"10.3389\/fmicb.2017.02682","article-title":"Arginine and polyamines fate in Leishmania infection","volume":"8","author":"Muxel","year":"2017","journal-title":"Front. Microbiol."},{"key":"2026091810035709500_bib55","doi-asserted-by":"publisher","first-page":"24484","DOI":"10.1074\/jbc.M115.678243","article-title":"AMP-activated protein kinase suppresses arachidonate 15-lipoxygenase expression in interleukin 4-polarized human macrophages","volume":"290","author":"Namgaladze","year":"2015","journal-title":"J. Biol. Chem."},{"key":"2026091810035709500_bib56","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1038\/s41586-022-05660-7","article-title":"Neonatal imprinting of alveolar macrophages via neutrophil-derived 12-HETE","volume":"614","author":"Pernet","year":"2023","journal-title":"Nature"},{"key":"2026091810035709500_bib57","doi-asserted-by":"publisher","DOI":"10.1111\/pim.12722","article-title":"Arginase and its mechanisms in Leishmania persistence","volume":"42","author":"Pessenda","year":"2020","journal-title":"Parasite Immunol."},{"key":"2026091810035709500_bib58","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/j.chembiol.2018.04.017","article-title":"PD(n-3 DPA) pathway regulates human monocyte differentiation and macrophage function","volume":"25","author":"Pistorius","year":"2018","journal-title":"Cell Chem Biol"},{"key":"2026091810035709500_bib59","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1007\/s004360100419","article-title":"Parasite-specific antibody and cellular immune responses in human infected with Necator americanus and Oesophagostomum bifurcum","volume":"87","author":"Pit","year":"2001","journal-title":"Parasitol. Res."},{"key":"2026091810035709500_bib60","doi-asserted-by":"publisher","DOI":"10.5281\/zenodo.3767371","article-title":"Laxy genomics pipelines","author":"Powell","year":"2020","journal-title":"Zenodo"},{"key":"2026091810035709500_bib61","doi-asserted-by":"publisher","DOI":"10.5281\/zenodo.3258932","article-title":"Degust: Interactive Rna-seq analysis","author":"Powell","year":"2026","journal-title":"Zenodo"},{"key":"2026091810035709500_bib62","doi-asserted-by":"publisher","DOI":"10.1101\/2023.10.30.563174","article-title":"CZ CELL\u00d7GENE discover: A single-cell data platform for scalable exploration, analysis and modeling of aggregated data","author":"CZI Single-Cell Biology Program","year":"2023","journal-title":"bioRxiv"},{"key":"2026091810035709500_bib63","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1086\/422256","article-title":"Immune responses in human necatoriasis: Association between interleukin-5 responses and resistance to reinfection","volume":"190","author":"Quinnell","year":"2004","journal-title":"J. Infect. Dis."},{"key":"2026091810035709500_bib64","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1002\/eji.201040801","article-title":"Saturated-efferocytosis generates pro-resolving CD11b low macrophages: Modulation by resolvins and glucocorticoids","volume":"41","author":"Schif-Zuck","year":"2011","journal-title":"Eur. J. Immunol."},{"key":"2026091810035709500_bib65","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"2026091810035709500_bib66","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1016\/j.celrep.2016.04.001","article-title":"TNF-mediated restriction of arginase 1 expression in myeloid cells triggers type 2 NO synthase activity at the site of infection","volume":"15","author":"Schleicher","year":"2016","journal-title":"Cell Rep."},{"key":"2026091810035709500_bib67","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/s41419-023-05622-5","article-title":"Tissue transglutaminase exacerbates renal fibrosis via alternative activation of monocyte-derived macrophages","volume":"14","author":"Shinoda","year":"2023","journal-title":"Cell Death Dis."},{"key":"2026091810035709500_bib68","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1038\/s41418-020-00652-4","article-title":"Efferocytosis potentiates the expression of arachidonate 15-lipoxygenase (ALOX15) in alternatively activated human macrophages through LXR activation","volume":"28","author":"Snodgrass","year":"2021","journal-title":"Cell Death Differ."},{"key":"2026091810035709500_bib69","doi-asserted-by":"publisher","first-page":"719","DOI":"10.3389\/fphar.2019.00719","article-title":"Regulation and functions of 15-Lipoxygenases in human macrophages","volume":"10","author":"Snodgrass","year":"2019","journal-title":"Front. Pharmacol."},{"key":"2026091810035709500_bib70","doi-asserted-by":"publisher","first-page":"1906","DOI":"10.3389\/fimmu.2018.01906","article-title":"A novel function for 15-Lipoxygenases in cholesterol homeostasis and CCL17 production in human macrophages","volume":"9","author":"Snodgrass","year":"2018","journal-title":"Front. Immunol."},{"key":"2026091810035709500_bib71","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1038\/s41590-019-0352-y","article-title":"The lung environment controls alveolar macrophage metabolism and responsiveness in type 2 inflammation","volume":"20","author":"Svedberg","year":"2019","journal-title":"Nat. Immunol."},{"key":"2026091810035709500_bib72","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2021"},{"key":"2026091810035709500_bib73","doi-asserted-by":"publisher","first-page":"479","DOI":"10.3389\/fimmu.2014.00479","article-title":"\u201cOf mice and men\u201d: Arginine metabolism in macrophages","volume":"5","author":"Thomas","year":"2014","journal-title":"Front. Immunol."},{"key":"2026091810035709500_bib74","doi-asserted-by":"publisher","first-page":"e93","DOI":"10.1182\/blood-2012-07-442640","article-title":"The biology of nematode- and IL4Ralpha-dependent murine macrophage polarization in vivo as defined by RNA-Seq and targeted lipidomics","volume":"120","author":"Thomas","year":"2012","journal-title":"Blood"},{"key":"2026091810035709500_bib75","doi-asserted-by":"publisher","first-page":"2529","DOI":"10.3389\/fimmu.2018.02529","article-title":"Macrophage polarization in Leishmaniasis: Broadening horizons","volume":"9","author":"Tomiotto-Pellissier","year":"2018","journal-title":"Front. Immunol."},{"key":"2026091810035709500_bib76","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1038\/s41586-020-2922-4","article-title":"A molecular cell atlas of the human lung from single-cell RNA sequencing","volume":"587","author":"Travaglini","year":"2020","journal-title":"Nature"},{"key":"2026091810035709500_bib77","doi-asserted-by":"publisher","first-page":"583","DOI":"10.21105\/joss.00583","article-title":"RNAsik: A pipeline for complete and reproducible RNA-seq analysis that runs anywhere with speed and ease","volume":"3","author":"Tsyganov","year":"2018","journal-title":"J. Open Source Softw."},{"key":"2026091810035709500_bib78","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1016\/j.immuni.2012.03.010","article-title":"12\/15-lipoxygenase orchestrates the clearance of apoptotic cells and maintains immunologic tolerance","volume":"36","author":"Uderhardt","year":"2012","journal-title":"Immunity"},{"key":"2026091810035709500_bib79","doi-asserted-by":"publisher","first-page":"53424","DOI":"10.3791\/53424","article-title":"Metabolic characterization of polarized M1 and M2 bone marrow-derived macrophages using real-time extracellular flux analysis","volume":"28","author":"Van den Bossche","year":"2015","journal-title":"J. Vis. Exp."},{"key":"2026091810035709500_bib80","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.it.2017.03.001","article-title":"Macrophage immunometabolism: Where are We (going)?","volume":"38","author":"Van den Bossche","year":"2017","journal-title":"Trends Immunol."},{"key":"2026091810035709500_bib81","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s12026-007-8012-y","article-title":"L-arginine metabolism and its impact on host immunity against Leishmania infection","volume":"41","author":"Wanasen","year":"2008","journal-title":"Immunol. Res."},{"key":"2026091810035709500_bib82","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/s41467-017-02538-5","article-title":"Human macrophages differentially produce specific resolvin or leukotriene signals that depend on bacterial pathogenicity","volume":"9","author":"Werz","year":"2018","journal-title":"Nat. Commun."},{"key":"2026091810035709500_bib83","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011296","article-title":"Th2-dependent STAT6-regulated genes in intestinal epithelial cells mediate larval trapping during secondary Heligmosomoides polygyrus bakeri infection","volume":"19","author":"Westermann","year":"2023","journal-title":"PLoS Pathog."},{"key":"2026091810035709500_bib84","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-24277-4","volume-title":"ggplot2: Elegant Graphics for Data Analysis","author":"Wickham","year":"2016"},{"key":"2026091810035709500_bib85","doi-asserted-by":"publisher","first-page":"giaa151","DOI":"10.1093\/gigascience\/giaa151","article-title":"SoupX removes ambient RNA contamination from droplet-based single-cell RNA sequencing data","volume":"9","author":"Young","year":"2020","journal-title":"Gigascience"},{"key":"2026091810035709500_bib86","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat. Commun."}],"container-title":["Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20241620\/2041118\/jem_20241620.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20241620\/2041118\/jem_20241620.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T14:04:16Z","timestamp":1789740256000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/223\/10\/e20241620\/283025\/Alox15-restrains-glycolysis-to-support-M2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,18]]},"references-count":87,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10,5]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20241620","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,18]]},"article-number":"e20241620"}}