{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:07:07Z","timestamp":1791079627771,"version":"4.1.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Eosinophils play important roles in regulation of cellular responses under conditions of homeostasis or infection. Intestinal infection with the parasitic nematode, Trichinella spiralis, induces a pronounced eosinophilia that coincides with establishment of larval stages in skeletal muscle. We have shown previously that in mouse strains in which the eosinophil lineage is ablated, large numbers of T. spiralis larvae are killed by NO, implicating the eosinophil as an immune regulator. In this report, we show that parasite death in eosinophil-ablated mice correlates with reduced recruitment of IL-4+ T cells and enhanced recruitment of inducible NO synthase (iNOS)-producing neutrophils to infected muscle, as well as increased iNOS in local F4\/80+CD11b+Ly6C+ macrophages. Actively growing T. spiralis larvae were susceptible to killing by NO in vitro, whereas mature larvae were highly resistant. Growth of larvae was impaired in eosinophil-ablated mice, potentially extending the period of susceptibility to the effects of NO and enhancing parasite clearance. Transfer of eosinophils into eosinophil-ablated \u0394dblGATA mice restored larval growth and survival. Regulation of immunity was not dependent upon eosinophil peroxidase or major basic protein 1 and did not correlate with activity of the IDO pathway. Our results suggest that eosinophils support parasite growth and survival by promoting accumulation of Th2 cells and preventing induction of iNOS in macrophages and neutrophils. These findings begin to define the cellular interactions that occur at an extraintestinal site of nematode infection in which the eosinophil functions as a pivotal regulator of immunity.<\/jats:p>","DOI":"10.4049\/jimmunol.1101980","type":"journal-article","created":{"date-parts":[[2011,12,2]],"date-time":"2011-12-02T05:55:46Z","timestamp":1322805346000},"page":"417-425","source":"Crossref","is-referenced-by-count":100,"title":["Eosinophils Preserve Parasitic Nematode Larvae by Regulating Local Immunity"],"prefix":"10.1093","volume":"188","author":[{"given":"Nebiat G","family":"Gebreselassie","sequence":"first","affiliation":[{"name":"Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University , Ithaca, NY 14853"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R","family":"Moorhead","sequence":"additional","affiliation":[{"name":"Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University , Ithaca, NY 14853"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Fabre","sequence":"additional","affiliation":[{"name":"Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University , Ithaca, NY 14853"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucille F","family":"Gagliardo","sequence":"additional","affiliation":[{"name":"Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University , Ithaca, NY 14853"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy A","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona , Scottsdale, AZ 85259"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona , Scottsdale, AZ 85259"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith A","family":"Appleton","sequence":"additional","affiliation":[{"name":"Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University , Ithaca, NY 14853"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,1,1]]},"reference":[{"key":"2025032409432782300_r1","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1084\/jem.20091903","article-title":"Regulation of pathogenesis and immunity in helminth infections","volume":"206","author":"Maizels","year":"2009","journal-title":"J. Exp. Med."},{"key":"2025032409432782300_r2","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1128\/iai.41.1.445-447.1983","article-title":"Delayed expulsion of adult Trichinella spiralis by mast cell-deficient W\/Wv mice","volume":"41","author":"Ha","year":"1983","journal-title":"Infect. Immun."},{"key":"2025032409432782300_r3","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1046\/j.1365-3024.2000.00270.x","article-title":"Mucosal mast cell responses are not required for protection against infection with the murine nematode parasite Trichuris muris","volume":"22","author":"Koyama","year":"2000","journal-title":"Parasite Immunol."},{"key":"2025032409432782300_r4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-3024.1983.tb00718.x","article-title":"Kinetics of expulsion of the nematode, Nippostrongylus brasiliensis, in mast-cell deficient W\/WV mice","volume":"5","author":"Mitchell","year":"1983","journal-title":"Parasite Immunol."},{"key":"2025032409432782300_r5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-3024.2010.01246.x","article-title":"Accumulation of eosinophils in intestine-draining mesenteric lymph nodes occurs after Trichuris muris infection","author":"Svensson","year":"2011","journal-title":"Parasite Immunol."},{"key":"2025032409432782300_r6","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1182\/blood-2006-04-015933","article-title":"Schistosoma mansoni infection in eosinophil lineage-ablated mice","volume":"108","author":"Swartz","year":"2006","journal-title":"Blood"},{"key":"2025032409432782300_r7","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.4049\/jimmunol.182.3.1577","article-title":"Eosinophil deficiency compromises parasite survival in chronic nematode infection","volume":"182","author":"Fabre","year":"2009","journal-title":"J. Immunol."},{"key":"2025032409432782300_r8","doi-asserted-by":"crossref","first-page":"5236","DOI":"10.1128\/IAI.00329-06","article-title":"Lack of eosinophil peroxidase or major basic protein impairs defense against murine filarial infection","volume":"74","author":"Specht","year":"2006","journal-title":"Infect. Immun."},{"key":"2025032409432782300_r9","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/j.ijpara.2007.04.006","article-title":"Impaired resistance in early secondary Nippostrongylus brasiliensis infections in mice with defective eosinophilopoeisis","volume":"37","author":"Knott","year":"2007","journal-title":"Int. J. Parasitol."},{"key":"2025032409432782300_r10","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.4049\/jimmunol.178.2.1039","article-title":"Coordinated control of immunity to muscle stage Trichinella spiralis by IL-10, regulatory T cells, and TGF-beta","volume":"178","author":"Beiting","year":"2007","journal-title":"J. Immunol."},{"key":"2025032409432782300_r11","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1126\/science.1100283","article-title":"A critical role for eosinophils in allergic airways remodeling","volume":"305","author":"Humbles","year":"2004","journal-title":"Science"},{"key":"2025032409432782300_r12","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1126\/science.1099472","article-title":"Defining a link with asthma in mice congenitally deficient in eosinophils","volume":"305","author":"Lee","year":"2004","journal-title":"Science"},{"key":"2025032409432782300_r13","doi-asserted-by":"crossref","first-page":"5509","DOI":"10.4049\/jimmunol.165.10.5509","article-title":"Eosinophil major basic protein-1 does not contribute to allergen-induced airway pathologies in mouse models of asthma","volume":"165","author":"Denzler","year":"2000","journal-title":"J. Immunol."},{"key":"2025032409432782300_r14","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.4049\/jimmunol.167.3.1672","article-title":"Extensive eosinophil degranulation and peroxidase-mediated oxidation of airway proteins do not occur in a mouse ovalbumin-challenge model of pulmonary inflammation","volume":"167","author":"Denzler","year":"2001","journal-title":"J. Immunol."},{"key":"2025032409432782300_r15","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.1128\/IAI.72.6.3129-3137.2004","article-title":"Interleukin-10 limits local and body cavity inflammation during infection with muscle-stage Trichinella spiralis","volume":"72","author":"Beiting","year":"2004","journal-title":"Infect. Immun."},{"key":"2025032409432782300_r16","first-page":"787","article-title":"Immunity to Trichinella spiralis. I. Transfer of resistance by two classes of lymphocytes","volume":"33","author":"Crum","year":"1977","journal-title":"Immunology"},{"key":"2025032409432782300_r17","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0166-6851(93)90090-K","article-title":"Identification of potential antigenic targets for rapid expulsion of Trichinella spiralis","volume":"58","author":"Appleton","year":"1993","journal-title":"Mol. Biochem. Parasitol."},{"key":"2025032409432782300_r18","doi-asserted-by":"crossref","first-page":"5909","DOI":"10.4049\/jimmunol.173.10.5909","article-title":"Cutting edge: human eosinophils regulate T cell subset selection through indoleamine 2,3-dioxygenase","volume":"173","author":"Odemuyiwa","year":"2004","journal-title":"J. Immunol."},{"key":"2025032409432782300_r19","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0014-4894(71)90064-6","article-title":"Trichinella spiralis: migration of larvae in the rat","volume":"30","author":"Harley","year":"1971","journal-title":"Exp. Parasitol."},{"key":"2025032409432782300_r20","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S1074-7613(03)00174-2","article-title":"Blood monocytes consist of two principal subsets with distinct migratory properties","volume":"19","author":"Geissmann","year":"2003","journal-title":"Immunity"},{"key":"2025032409432782300_r21","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1126\/science.1201475","article-title":"Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis","volume":"332","author":"Wu","year":"2011","journal-title":"Science"},{"key":"2025032409432782300_r22","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1126\/science.1204351","article-title":"Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation","volume":"332","author":"Jenkins","year":"2011","journal-title":"Science"},{"key":"2025032409432782300_r23","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/0014-4894(75)90058-2","article-title":"Trichinella spiralis: growth of the intracellular (muscle) larva","volume":"37","author":"Despommier","year":"1975","journal-title":"Exp. Parasitol."},{"key":"2025032409432782300_r24","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1016\/S0020-7519(98)00107-6","article-title":"Resistance of filarial nematode parasites to oxidative stress","volume":"28","author":"Selkirk","year":"1998","journal-title":"Int. J. Parasitol."},{"key":"2025032409432782300_r25","doi-asserted-by":"crossref","first-page":"3351","DOI":"10.1128\/iai.64.8.3351-3353.1996","article-title":"Role of nitric oxide in host defense against an extracellular, metazoan parasite, Brugia malayi","volume":"64","author":"Rajan","year":"1996","journal-title":"Infect. Immun."},{"key":"2025032409432782300_r26","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1073\/pnas.91.3.999","article-title":"Endothelial cells are activated by cytokine treatment to kill an intravascular parasite, Schistosoma mansoni, through the production of nitric oxide","volume":"91","author":"Oswald","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032409432782300_r27","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1128\/iai.65.1.219-226.1997","article-title":"Developmental differences determine larval susceptibility to nitric oxide-mediated killing in a murine model of vaccination against Schistosoma mansoni","volume":"65","author":"Ahmed","year":"1997","journal-title":"Infect. Immun."},{"key":"2025032409432782300_r28","doi-asserted-by":"crossref","first-page":"33","DOI":"10.18388\/abp.2006_3361","article-title":"Molecules released by helminth parasites involved in host colonization","volume":"53","author":"Dzik","year":"2006","journal-title":"Acta Biochim. Pol."},{"key":"2025032409432782300_r29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0166-6851(84)90013-6","article-title":"Scavenger enzymes and resistance to oxygen mediated damage in Trichinella spiralis","volume":"10","author":"Kazura","year":"1984","journal-title":"Mol. Biochem. Parasitol."},{"key":"2025032409432782300_r30","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.vetpar.2005.05.023","article-title":"Expressed sequence tags from life cycle stages of Trichinella spiralis: application to biology and parasite control","volume":"132","author":"Mitreva","year":"2005","journal-title":"Vet. Parasitol."},{"key":"2025032409432782300_r31","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.molbiopara.2004.05.015","article-title":"Gene discovery in the adenophorean nematode Trichinella spiralis: an analysis of transcription from three life cycle stages","volume":"137","author":"Mitreva","year":"2004","journal-title":"Mol. Biochem. Parasitol."},{"key":"2025032409432782300_r32","doi-asserted-by":"crossref","first-page":"e1000892","DOI":"10.1371\/journal.ppat.1000892","article-title":"Blood fluke exploitation of non-cognate CD4+ T cell help to facilitate parasite development","volume":"6","author":"Lamb","year":"2010","journal-title":"PLoS Pathog."},{"key":"2025032409432782300_r33","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.4049\/jimmunol.161.3.1428","article-title":"Host NK cells are required for the growth of the human filarial parasite Brugia malayi in mice","volume":"161","author":"Babu","year":"1998","journal-title":"J. Immunol."},{"key":"2025032409432782300_r34","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1006\/expr.1999.4438","article-title":"T cells facilitate Brugia malayi development in TCRalpha(null) mice","volume":"93","author":"Babu","year":"1999","journal-title":"Exp. Parasitol."},{"key":"2025032409432782300_r35","doi-asserted-by":"crossref","first-page":"e1000525","DOI":"10.1371\/journal.pbio.1000525","article-title":"Filarial parasites develop faster and reproduce earlier in response to host immune effectors that determine filarial life expectancy","volume":"8","author":"Babayan","year":"2010","journal-title":"PLoS Biol."},{"key":"2025032409432782300_r36","doi-asserted-by":"crossref","first-page":"472","DOI":"10.2307\/3283370","article-title":"Trichinella spiralis and the concept of niche","volume":"79","author":"Despommier","year":"1993","journal-title":"J. Parasitol."},{"key":"2025032409432782300_r37","doi-asserted-by":"crossref","first-page":"11238","DOI":"10.1158\/0008-5472.CAN-06-1278","article-title":"Macrophages regulate the angiogenic switch in a mouse model of breast cancer","volume":"66","author":"Lin","year":"2006","journal-title":"Cancer Res."},{"key":"2025032409432782300_r38","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1165\/ajrcmb.17.1.2796","article-title":"Expression of vascular endothelial growth factor by human eosinophils: upregulation by granulocyte macrophage colony-stimulating factor and interleukin-5","volume":"17","author":"Horiuchi","year":"1997","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2025032409432782300_r39","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1476-7961-8-10","article-title":"Hypoxia modulates human eosinophil function","volume":"8","author":"Nissim Ben Efraim","year":"2010","journal-title":"Clin. Mol. Allergy"},{"key":"2025032409432782300_r40","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.biocel.2004.09.001","article-title":"Human peripheral blood eosinophils induce angiogenesis","volume":"37","author":"Puxeddu","year":"2005","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"2025032409432782300_r41","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S0169-4758(98)01287-3","article-title":"How does Trichinella spiralis make itself at home?","volume":"14","author":"Despommier","year":"1998","journal-title":"Parasitol. Today"},{"key":"2025032409432782300_r42","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1084\/jem.20062027","article-title":"Eosinophil-derived neurotoxin acts as an alarmin to activate the TLR2-MyD88 signal pathway in dendritic cells and enhances Th2 immune responses","volume":"205","author":"Yang","year":"2008","journal-title":"J. Exp. Med."},{"key":"2025032409432782300_r43","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1084\/jem.20040590","article-title":"Basophils produce IL-4 and accumulate in tissues after infection with a Th2-inducing parasite","volume":"200","author":"Min","year":"2004","journal-title":"J. Exp. Med."},{"key":"2025032409432782300_r44","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1084\/jem.20071836","article-title":"Strain-specific requirement for eosinophils in the recruitment of T cells to the lung during the development of allergic asthma","volume":"205","author":"Walsh","year":"2008","journal-title":"J. Exp. Med."},{"key":"2025032409432782300_r45","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1084\/jem.20071840","article-title":"Allergic pulmonary inflammation in mice is dependent on eosinophil-induced recruitment of effector T cells","volume":"205","author":"Jacobsen","year":"2008","journal-title":"J. Exp. Med."},{"key":"2025032409432782300_r46","doi-asserted-by":"crossref","first-page":"16418","DOI":"10.1073\/pnas.0607863103","article-title":"A central regulatory role for eosinophils and the eotaxin\/CCR3 axis in chronic experimental allergic airway inflammation","volume":"103","author":"Fulkerson","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032409432782300_r47","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.4049\/jimmunol.1001148","article-title":"Computational and experimental analysis reveals a requirement for eosinophil-derived IL-13 for the development of allergic airway responses in C57BL\/6 mice","volume":"186","author":"Walsh","year":"2011","journal-title":"J. Immunol."},{"key":"2025032409432782300_r48","doi-asserted-by":"crossref","first-page":"7585","DOI":"10.4049\/jimmunol.179.11.7585","article-title":"Airway eosinophils: allergic inflammation recruited professional antigen-presenting cells","volume":"179","author":"Wang","year":"2007","journal-title":"J. Immunol."},{"key":"2025032409432782300_r49","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1086\/522968","article-title":"Eosinophils act as antigen-presenting cells to induce immunity to Strongyloides stercoralis in mice","volume":"196","author":"Padigel","year":"2007","journal-title":"J. Infect. Dis."},{"key":"2025032409432782300_r50","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.4049\/jimmunol.174.2.1063","article-title":"Mast cells, basophils, and eosinophils acquire constitutive IL-4 and IL-13 transcripts during lineage differentiation that are sufficient for rapid cytokine production","volume":"174","author":"Gessner","year":"2005","journal-title":"J. Immunol."},{"key":"2025032409432782300_r51","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1146\/annurev.immunol.24.021605.090720","article-title":"The eosinophil","volume":"24","author":"Rothenberg","year":"2006","journal-title":"Annu. Rev. Immunol."},{"key":"2025032409432782300_r52","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1046\/j.1365-3024.2000.00328.x","article-title":"Interleukin-5 deficient mice exhibit impaired host defence against challenge Trichinella spiralis infections","volume":"22","author":"Vallance","year":"2000","journal-title":"Parasite Immunol."},{"key":"2025032409432782300_r53","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.2307\/3284385","article-title":"Marked eosinophilia in interleukin-5 transgenic mice fails to prevent Trichinella spiralis infection","volume":"83","author":"Hokibara","year":"1997","journal-title":"J. Parasitol."},{"key":"2025032409432782300_r54","doi-asserted-by":"crossref","first-page":"3642","DOI":"10.4049\/jimmunol.149.11.3642","article-title":"Depletion of eosinophils by anti-IL-5 monoclonal antibody treatment of mice infected with Trichinella spiralis does not alter parasite burden or immunologic resistance to reinfection","volume":"149","author":"Herndon","year":"1992","journal-title":"J. Immunol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/188\/1\/417\/61615833\/1101980.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/188\/1\/417\/61615833\/1101980.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T07:32:08Z","timestamp":1743060728000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/188\/1\/417\/7978184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1,1]]},"references-count":54,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,1,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1101980","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2012,1]]},"published":{"date-parts":[[2012,1,1]]}}}