{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:25:46Z","timestamp":1760235946805,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T00:00:00Z","timestamp":1633478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["315817 and A-1-S 37879"],"award-info":[{"award-number":["315817 and A-1-S 37879"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Signal Transducer and Activator of Transcription (STAT) 1 signaling is critical for IFN-\u03b3-mediated immune responses and resistance to protozoan and viral infections. However, its role in immunoregulation during helminth parasitic infections is not fully understood. Here, we used STAT1\u2212\/\u2212 mice to investigate the role of this transcription factor during a helminth infection caused by the cestode Taenia crassiceps and show that STAT1 is a central molecule favoring susceptibility to this infection. STAT1\u2212\/\u2212 mice displayed lower parasite burdens at 8 weeks post-infection compared to STAT1+\/+ mice. STAT1 mediated the recruitment of inflammatory monocytes and the development of alternatively activated macrophages (M2) at the site of infection. The absence of STAT1 prevented the recruitment of CD11b+Ly6ChiLy6G\u2212 monocytic cells and therefore their suppressive activity. This failure was associated with the defective expression of CCR2 on CD11b+Ly6ChiLy6G\u2212 cells. Importantly, CD11b+Ly6ChiLy6G\u2212 cells highly expressed PDL-1 and suppressed T-cell proliferation elicited by anti-CD3 stimulation. PDL-1+ cells were mostly absent in STAT1\u2212\/\u2212 mice. Furthermore, only STAT1+\/+ mice developed M2 macrophages at 8 weeks post-infection, although macrophages from both T. crassiceps-infected STAT1+\/+ and STAT1\u2212\/\u2212 mice responded to IL-4 in vitro, and both groups of mice were able to produce the Th2 cytokine IL-13. This suggests that CD11b+CCR2+Ly6ChiLy6G\u2212 cells give rise to M2 macrophages in this infection. In summary, a lack of STAT1 resulted in impaired recruitment of CD11b+CCR2+Ly6ChiLy6G\u2212 cells, failure to develop M2 macrophages, and increased resistance against T. crassiceps infection.<\/jats:p>","DOI":"10.3390\/pathogens10101287","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T21:26:20Z","timestamp":1633728380000},"page":"1287","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["STAT1-Dependent Recruitment of Ly6ChiCCR2+ Inflammatory Monocytes and M2 Macrophages in a Helminth Infection"],"prefix":"10.3390","volume":"10","author":[{"given":"Mireya","family":"Becerra-D\u00edaz","sequence":"first","affiliation":[{"name":"Unidad de Biomedicina, Facultad de Estudios Superiores (FES)-Iztacala, Universidad Nacional Aut\u00f3noma de Mexico (UNAM), Av. De Los Barrios, Los Reyes Iztacala, Tlalnepantla 54090, Edo. de Mexico, Mexico"},{"name":"Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yadira","family":"Ledesma-Soto","sequence":"additional","affiliation":[{"name":"Unidad de Biomedicina, Facultad de Estudios Superiores (FES)-Iztacala, Universidad Nacional Aut\u00f3noma de Mexico (UNAM), Av. De Los Barrios, Los Reyes Iztacala, Tlalnepantla 54090, Edo. de Mexico, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonadab E.","family":"Olgu\u00edn","sequence":"additional","affiliation":[{"name":"Unidad de Biomedicina, Facultad de Estudios Superiores (FES)-Iztacala, Universidad Nacional Aut\u00f3noma de Mexico (UNAM), Av. De Los Barrios, Los Reyes Iztacala, Tlalnepantla 54090, Edo. de Mexico, Mexico"},{"name":"Laboratorio Nacional en Salud FES-Iztacala, Universidad Nacional Aut\u00f3noma de Mexico (UNAM), Av. De Los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, Edo. de Mexico, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angel","family":"S\u00e1nchez-Barrera","sequence":"additional","affiliation":[{"name":"Unidad de Biomedicina, Facultad de Estudios Superiores (FES)-Iztacala, Universidad Nacional Aut\u00f3noma de Mexico (UNAM), Av. De Los Barrios, Los Reyes Iztacala, Tlalnepantla 54090, Edo. de Mexico, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3056-9997","authenticated-orcid":false,"given":"M\u00f3nica G.","family":"Mendoza-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Unidad de Biomedicina, Facultad de Estudios Superiores (FES)-Iztacala, Universidad Nacional Aut\u00f3noma de Mexico (UNAM), Av. De Los Barrios, Los Reyes Iztacala, Tlalnepantla 54090, Edo. de Mexico, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandy","family":"Reyes","sequence":"additional","affiliation":[{"name":"Unidad de Biomedicina, Facultad de Estudios Superiores (FES)-Iztacala, Universidad Nacional Aut\u00f3noma de Mexico (UNAM), Av. De Los Barrios, Los Reyes Iztacala, Tlalnepantla 54090, Edo. de Mexico, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhay R.","family":"Satoskar","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis I.","family":"Terrazas","sequence":"additional","affiliation":[{"name":"Unidad de Biomedicina, Facultad de Estudios Superiores (FES)-Iztacala, Universidad Nacional Aut\u00f3noma de Mexico (UNAM), Av. De Los Barrios, Los Reyes Iztacala, Tlalnepantla 54090, Edo. de Mexico, Mexico"},{"name":"Laboratorio Nacional en Salud FES-Iztacala, Universidad Nacional Aut\u00f3noma de Mexico (UNAM), Av. De Los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, Edo. de Mexico, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.7150\/ijbs.7.1371","article-title":"Signal Transducers and Activators of Transcription (STAT) family members in helminth infections","volume":"7","author":"Terrazas","year":"2011","journal-title":"Int. J. Biol. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1172\/JCI0215770","article-title":"IFNs and STATs in innate immunity to microorganisms","volume":"109","author":"Decker","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_3","first-page":"13","article-title":"T helper differentiation proceeds through Stat1-dependent, Stat4-dependent and Stat4-independent phases","volume":"238","author":"Murphy","year":"1999","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1128\/IAI.72.3.1257-1264.2004","article-title":"STAT1 is essential for antimicrobial effector function but dispensable for gamma interferon production during Toxoplasma gondii infection","volume":"72","author":"Gavrilescu","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.it.2004.09.015","article-title":"The chemokine system in diverse forms of macrophage activation and polarization","volume":"25","author":"Mantovani","year":"2004","journal-title":"Trends Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1002\/eji.200323163","article-title":"Development of protective immunity against cutaneous leishmaniasis is dependent on STAT1-mediated IFN signaling pathway","volume":"33","author":"Rosas","year":"2003","journal-title":"Eur. J. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ijpara.2004.10.018","article-title":"Leishmania inhibits STAT1-mediated IFN-gamma signaling in macrophages: Increased tyrosine phosphorylation of dominant negative STAT1beta by Leishmania mexicana","volume":"35","author":"Bhardwaj","year":"2005","journal-title":"Int. J. Parasitol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/imm.12438","article-title":"Signal transducer and activator of transcription 1 (STAT-1) plays a critical role in control of Trypanosoma cruzi infection","volume":"145","author":"Kulkarni","year":"2015","journal-title":"Immunology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"383","DOI":"10.2174\/156802608783790848","article-title":"The complex role of pro- and anti-inflammatory cytokines in cysticercosis: Immunological lessons from experimental and natural hosts","volume":"8","author":"Terrazas","year":"2008","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s004360050522","article-title":"Th1-type cytokines improve resistance to murine cysticercosis caused by Taenia crassiceps","volume":"85","author":"Terrazas","year":"1999","journal-title":"Parasitol. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.4049\/jimmunol.168.7.3135","article-title":"Cutting edge: Susceptibility to the larval stage of the helminth parasite Taenia crassiceps is mediated by Th2 response induced via STAT6 signaling","volume":"168","author":"David","year":"2002","journal-title":"J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4552","DOI":"10.1128\/IAI.72.8.4552-4560.2004","article-title":"A STAT4-dependent Th1 response is required for resistance to the helminth parasite Taenia crassiceps","volume":"72","author":"Saavedra","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3656","DOI":"10.1128\/IAI.70.7.3656-3664.2002","article-title":"Chronic helminth infection induces alternatively activated macrophages expressing high levels of CCR5 with low interleukin-12 production and Th2-biasing ability","volume":"70","author":"Satoskar","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0014-4894(02)00028-0","article-title":"Taenia crassiceps: Androgen reconstitution of the host leads to protection during cysticercosis","volume":"100","author":"Baig","year":"2002","journal-title":"Exp. Parasitol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.ijpara.2014.03.012","article-title":"Taenia crassiceps infection and its excreted\/secreted products inhibit STAT1 activation in response to IFN-gamma","volume":"44","author":"Terrazas","year":"2014","journal-title":"Int. J. Parasitol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.ijpara.2009.11.014","article-title":"Early removal of alternatively activated macrophages leads to Taenia crassiceps cysticercosis clearance In Vivo","volume":"40","author":"Reyes","year":"2010","journal-title":"Int. J. Parasitol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1128\/IAI.00472-09","article-title":"Inflammatory monocytes but not neutrophils are necessary to control infection with Toxoplasma gondii in mice","volume":"78","author":"Dunay","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Terrazas, C., Varikuti, S., Oghumu, S., Steinkamp, H.M., Ardic, N., Kimble, J., Nakhasi, H., and Satoskar, A.R. (2017). Ly6C(hi) inflammatory monocytes promote susceptibility to Leishmania donovani infection. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-14935-3"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.jneuroim.2006.10.006","article-title":"PD-1\/PD-L1, but not PD-1\/PD-L2, interactions regulate the severity of experimental autoimmune encephalomyelitis","volume":"182","author":"Carter","year":"2007","journal-title":"J. Neuroimmunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1093\/intimm\/dxf076","article-title":"Immunosuppression during acute Trypanosoma cruzi infection: Involvement of Ly6G (Gr1(+))CD11b(+) immature myeloid suppressor cells","volume":"14","author":"Goni","year":"2002","journal-title":"Int. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1016\/j.ijpara.2005.06.003","article-title":"Role of the programmed Death-1 pathway in the suppressive activity of alternatively activated macrophages in experimental cysticercosis","volume":"35","author":"Terrazas","year":"2005","journal-title":"Int. J. Parasitol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5487","DOI":"10.1128\/IAI.72.9.5487-5492.2004","article-title":"Both expansion of regulatory GR1+ CD11b+ myeloid cells and anergy of T lymphocytes participate in hyporesponsiveness of the lung-associated immune system during acute toxoplasmosis","volume":"72","author":"Voisin","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1038\/nm1451","article-title":"Memory T(H)2 cells induce alternatively activated macrophages to mediate protection against nematode parasites","volume":"12","author":"Anthony","year":"2006","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.4049\/jimmunol.177.3.1393","article-title":"Novel effector molecules in type 2 inflammation: Lessons drawn from helminth infection and allergy","volume":"177","author":"Nair","year":"2006","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1053\/j.gastro.2008.03.077","article-title":"Th2 cytokine-induced alterations in intestinal smooth muscle function depend on alternatively activated macrophages","volume":"135","author":"Zhao","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6095","DOI":"10.4049\/jimmunol.174.10.6095","article-title":"Reactive oxygen species and 12\/15-lipoxygenase contribute to the antiproliferative capacity of alternatively activated myeloid cells elicited during helminth infection","volume":"174","author":"Brys","year":"2005","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1002\/stem.170138","article-title":"Functional roles of STAT family proteins: Lessons from knockout mice","volume":"17","author":"Akira","year":"1999","journal-title":"Stem Cells"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S0079-6107(98)00051-0","article-title":"The STAT family of proteins in cytokine signaling","volume":"71","author":"Shuai","year":"1999","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.biochi.2010.02.009","article-title":"STAT1 and pathogens, not a friendly relationship","volume":"92","author":"Najjar","year":"2010","journal-title":"Biochimie"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1126\/science.1281555","article-title":"Activation of transcription by IFN-gamma: Tyrosine phosphorylation of a 91-kD DNA binding protein","volume":"258","author":"Shuai","year":"1992","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3637","DOI":"10.4049\/jimmunol.175.6.3637","article-title":"IFN-gamma-primed macrophages exhibit increased CCR2-dependent migration and altered IFN-gamma responses mediated by Stat1","volume":"175","author":"Hu","year":"2005","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1084\/jem.186.10.1757","article-title":"Defects in macrophage recruitment and host defense in mice lacking the CCR2 chemokine receptor","volume":"186","author":"Kurihara","year":"1997","journal-title":"J. Exp. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"12053","DOI":"10.1073\/pnas.94.22.12053","article-title":"Severe reduction in leukocyte adhesion and monocyte extravasation in mice deficient in CC chemokine receptor 2","volume":"94","author":"Kuziel","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/ni.3734","article-title":"Vitamin A mediates conversion of monocyte-derived macrophages into tissue-resident macrophages during alternative activation","volume":"18","author":"Gundra","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4716","DOI":"10.4049\/jimmunol.1601860","article-title":"A Schistosoma japonicum Infection Promotes the Expansion of Myeloid-Derived Suppressor Cells by Activating the JAK\/STAT3 Pathway","volume":"198","author":"Yang","year":"2017","journal-title":"J. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.jmii.2019.12.001","article-title":"Schistosoma egg antigens suppress LPS-induced inflammation in human IMR-90 cells by modulation of JAK\/STAT1 signaling","volume":"54","author":"Lee","year":"2021","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1126\/science.1254517","article-title":"Helminth infection reactivates latent gamma-herpesvirus via cytokine competition at a viral promoter","volume":"345","author":"Reese","year":"2014","journal-title":"Science"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/10\/1287\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:09:57Z","timestamp":1760166597000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/10\/1287"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,6]]},"references-count":37,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["pathogens10101287"],"URL":"https:\/\/doi.org\/10.3390\/pathogens10101287","relation":{},"ISSN":["2076-0817"],"issn-type":[{"type":"electronic","value":"2076-0817"}],"subject":[],"published":{"date-parts":[[2021,10,6]]}}}