{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:55:41Z","timestamp":1791377741081,"version":"4.3.2"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T00:00:00Z","timestamp":1656460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["Grant# 421392\/2018-5"],"award-info":[{"award-number":["Grant# 421392\/2018-5"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007375","name":"Pr\u00f3-Reitoria de Pesquisa, Universidade Federal de Minas Gerais","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007375","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>IL-17 is a cytokine produced by innate and acquired immunity cells that have an action against fungi and bacteria. However, its action in helminth infections is unclear, including in <jats:italic>Toxocara canis<\/jats:italic> infection. Toxocariasis is a neglected zoonosis representing a significant public health problem with an estimated seroprevalence of 19% worldwide. In the present study, we describe the immunopathological action of IL-17RA in acute <jats:italic>T. canis<\/jats:italic> infection. C57BL\/6j (WT) and IL-17RA receptor knockout (IL-17RA-\/-) mice were infected with 1000 <jats:italic>T. canis<\/jats:italic> eggs. Mice were evaluated 3 days post-infection for parasite load and white blood cell count. Lung tissue was harvested for histopathology and cytokine expression. In addition, we performed multiparametric flow cytometry in the BAL and peripheral blood, evaluating phenotypic and functional changes in myeloid and lymphoid populations. We showed that IL-17RA is essential to control larvae load in the lung; however, IL-17RA contributed to pulmonary inflammation, inducing inflammatory nodular aggregates formation and presented higher pulmonary IL-6 levels. The absence of IL-17RA was associated with a higher frequency of neutrophils as a source of IL-4 in BAL, while in the presence of IL-17RA, mice display a higher frequency of alveolar macrophages expressing the same cytokine. Taken together, this study indicates that neutrophils may be an important source of IL-4 in the lungs during <jats:italic>T. canis<\/jats:italic> infection. Furthermore, IL-17\/IL-17RA axis is important to control parasite load, however, its presence triggers lung inflammation that can lead to tissue damage.<\/jats:p>","DOI":"10.3389\/fimmu.2022.864632","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T11:09:19Z","timestamp":1656500959000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["IL-17RA receptor signaling contributes to lung inflammation and parasite burden during Toxocara canis infection in mice"],"prefix":"10.3389","volume":"13","author":[{"given":"Tha\u00eds","family":"Leal-Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila de Almeida","family":"Lopes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flaviane","family":"Vieira-Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabr\u00edcio Marcus Silva","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Kraemer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiza de Lima Silva","family":"Padr\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara C\u00e1ssia Oliveira","family":"Amorim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge Lucas Nascimento","family":"Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remo Castro","family":"Russo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Toshio","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa Mour\u00e3o Dias","family":"Magalh\u00e3es","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian Lacerda","family":"Bueno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200839120","article-title":"Il-17-producing \u03b3\u03b4 t cells","volume":"39","author":"O\u2019Brien","year":"2009","journal-title":"Eur J Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00453","article-title":"Eosinophil-associated innate IL-17 response promotes aspergillus fumigatus lung pathology","volume":"9","author":"de Oliveira Malacco","year":"2019","journal-title":"Front Cell Infect Microbiol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1038\/nm.3423","article-title":"Interleukin-17-producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity","volume":"20","author":"Kim","year":"2014","journal-title":"Nat Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/nri2586.Structure","article-title":"Structure and signaling in the IL-17 receptor superfamily","volume":"9","author":"Gaffen","year":"2010","journal-title":"Nat Rev Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2019.102429","article-title":"Critical role of interleukin (IL)-17 in inflammatory and immune disorders: An updated review of the evidence focusing in controversies","volume":"19","author":"Ruiz de Morales","year":"2020","journal-title":"Autoimmun Rev"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxv017","article-title":"Lack of Il-17 signaling decreases liver fibrosis in murine schistosomiasis japonica","volume":"27","author":"Zhang","year":"2015","journal-title":"Int Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201041327","article-title":"Exacerbated egg-induced immunopathology in murine schistosoma mansoni infection is primarily mediated by IL-17 and restrained by IFN-\u03b3","volume":"41","author":"Rutitzky","year":"2011","journal-title":"Eur J Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2013.09.008","article-title":"Roles of Th17 cells in pulmonary granulomas induced by schistosoma japonicum in C57Bl\/6 mice","volume":"285","author":"Chen","year":"2013","journal-title":"Cell Immunol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pntd.0004382","article-title":"Multiple exposures to ascaris suum induce tissue injury and mixed Th2\/Th17 immune response in mice","volume":"10","author":"Nogueira","year":"2016","journal-title":"PloS Negl Trop Dis"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3023","article-title":"Chitinase-like proteins promote Il-17-mediated neutrophilia in a tradeoff between nematode killing and host damage","volume":"15","author":"Sutherland","year":"2014","journal-title":"Nat Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2628","article-title":"An essential role for T H 2-type responses in limiting acute tissue damage during experimental helminth infection","volume":"18","author":"Chen","year":"2012","journal-title":"Nat Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-020-0318-2","article-title":"Il-17a both initiates, via IFN\u03b3 suppression, and limits the pulmonary type-2 immune response to nematode infection","volume":"13","author":"Ajendra","year":"2020","journal-title":"Mucosal Immunol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1186\/s13071-015-0962-7","article-title":"New insights into the immunopathology of early toxocara canis infection in mice","volume":"8","author":"Resende","year":"2015","journal-title":"Parasites Vectors"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0009639","article-title":"Detrimental role of IL-33\/ST2 pathway sustaining a chronic eosinophil-dependent Th2 inflammatory response, tissue damage and parasite burden during toxocara canis infection in mice","volume":"15","author":"Leal-Silva","year":"2021","journal-title":"PloS Negl Trop Dis"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007809","article-title":"seroprevalence estimates for toxocariasis in people worldwide: A systematic review and meta-analysis","volume":"13","author":"Rostami","year":"2019","journal-title":"PloS Negl Trop Dis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30331-6","article-title":"Human toxocariasis","volume":"18","author":"Ma","year":"2018","journal-title":"Lancet Infect Dis"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2005.06.022","article-title":"Influence of murine toxocara canis infection on plasma and bronchoalveolar lavage fluid eosinophil numbers and its correlation with cytokine levels","volume":"134","author":"Pecinali","year":"2005","journal-title":"Vet. Parasitol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1515\/ap-2017-0099","article-title":"Humoral response of mice infected with toxocara canis following different infection schemes","volume":"62","author":"Nov\u00e1k","year":"2017","journal-title":"Acta Parasitol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pcbi.1005112","article-title":"Cytofkit: a bioconductor package for an integrated mass cytometry data analysis pipeline","volume":"12","author":"Chen","year":"2016","journal-title":"PloS Comput Biol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/pim.12672","article-title":"Immune response to chronic toxocara canis infection in a mice model","volume":"41","author":"Ruiz-Manzano","year":"2019","journal-title":"Parasite Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1602185","article-title":"IL-17 receptor a maintains and protects the skin barrier to prevent allergic skin inflammation","volume":"199","author":"Floudas","year":"2017","journal-title":"J Immunol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"79","DOI":"10.22579\/20112629.631","article-title":"Toxocariasis y vacunaci\u00f3n para toxocara: una revisi\u00f3n sistem\u00e1tica","volume":"24","author":"Jaramillo-Hern\u00e1ndez","year":"2020","journal-title":"Orinoquia"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1017\/s0031182022000075","article-title":"Tissue eosinophilia correlates with mice susceptibility, granuloma formation, and damage during toxocara canis infection","volume":"149","author":"Leal-Silva","year":"2022","journal-title":"Parasitology"},{"key":"B24","doi-asserted-by":"crossref","DOI":"10.1079\/9781845930264.0000","volume-title":"Toxocara: the enigmatic parasite","author":"Holland","year":"2006"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903162","article-title":"IL-17 Promotes p38 MAPK-dependent endothelial activation enhancing neutrophil recruitment to sites of inflammation","volume":"184","author":"Roussel","year":"2010","journal-title":"J Immunol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"439-56","DOI":"10.1146\/annurev-immunol-042617","article-title":"Nonclassical Monocytes in Health and Disease","volume":"37","author":"Babu Narasimhan","year":"2019","journal-title":"Annual Rev Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160499","article-title":"Autonomous TNF is critical for in vivo monocyte survival in steady state and inflammation","volume":"214","author":"Wol","year":"2017","journal-title":"J Exp Med"},{"key":"B28","doi-asserted-by":"publisher","first-page":"12","DOI":"10.4103\/ed.ed_23_18","article-title":"Seroprevalence of toxocara canis and the parasitic effect on plasma cytokines in children aged 6 to 11 years in saki-east local government area in nigeria","volume":"4","author":"Olaniyan","year":"2019","journal-title":"Environ Dis"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.24.021605.090720","article-title":"The eosinophil","volume":"24","author":"Rothenberg","year":"2006","journal-title":"Annu Rev Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.8.5625","article-title":"Molecular mechanisms of cytokine and chemokine release from eosinophils activated by IL-17A, IL-17F, and IL-23: implication for Th17 lymphocytes-mediated allergic inflammation","volume":"180","author":"Cheung","year":"2008","journal-title":"J Immunol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/ni.3049","article-title":"The immunology of asthma","volume":"16","author":"Lambrecht","year":"2015","journal-title":"Nat Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2797","article-title":"Activation of neutrophils by autocrine IL-17A-IL-17RC interactions during fungal infection is regulated by IL-6, IL-23, ROR\u03b3t and dectin-2","volume":"15","author":"Taylor","year":"2014","journal-title":"Nat Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2001.117929","article-title":"IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines","volume":"108","author":"Molet","year":"2001","journal-title":"J Allergy Clin Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009891","article-title":"Lung eosinophils elicited during allergic and acute aspergillosis express ROR\u03eat and IL-23R but do not require IL-23 for IL-17 production","author":"Yadav","year":"2021","journal-title":"PloS Pathog"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006175","article-title":"Central role of IL-23 and IL-17 producing eosinophils as immunomodulatory effector cells in acute pulmonary aspergillosis and allergic asthma","author":"Guerra","year":"2017","journal-title":"PloS Pathog"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1015476108","article-title":"TNF-\u03b1 from inflammatory dendritic cells (DCs) regulates lung IL-17A\/IL-5 levels and neutrophilia versus eosinophilia during persistent fungal infection","volume":"108","author":"Fei","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"B37","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.ebiom.2017.08.001","article-title":"IL-17 production of neutrophils enhances antibacteria ability but promotes arthritis development during mycobacterium tuberculosis infection","volume":"23","author":"Hu","year":"2017","journal-title":"EBioMedicine"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1172\/JCI38702","article-title":"IL-17 produced by neutrophils regulates IFN-\u03b3-mediated neutrophil migration in mouse kidney ischemia-reperfusion injury","volume":"120","author":"Li","year":"2010","journal-title":"J Clin Invest"},{"key":"B39","doi-asserted-by":"publisher","first-page":"490","DOI":"10.4049\/jimmunol.1100123","article-title":"Mast Cells and Neutrophils Release IL-17 through Extracellular Trap Formation in Psoriasis","volume":"187","author":"Lin","year":"2011","journal-title":"J Immunol"},{"key":"B40","doi-asserted-by":"crossref","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":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00064","article-title":"Robust phenotypic activation of eosinophils during experimental toxocara canis infection","volume":"9","author":"de Almeida Rodolpho","year":"2018","journal-title":"Front Immunol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"3590","DOI":"10.1093\/eurheartj\/ehx517","article-title":"CD27 co-stimulation increases the abundance of regulatory T cells and reduces atherosclerosis in hyperlipidaemic mice","volume":"38","author":"Winkels","year":"2017","journal-title":"Eur Heart J"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201646837","article-title":"CD69: from activation marker to metabolic gatekeeper","volume":"47","author":"Cibri\u00e1n","year":"2017","journal-title":"Eur J Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.00456-10","article-title":"CD69 Association with Jak3\/Stat5 proteins regulates Th17 cell differentiation","volume":"30","author":"Mart\u00edn","year":"2010","journal-title":"Mol Cell Biol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2005.02250.x","article-title":"Persistent airway hyper-responsiveness and inflammation in toxocara canis-infected BALB\/c mice","volume":"35","author":"Pinelli","year":"2005","journal-title":"Clin Exp Allergy"},{"key":"B46","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1146\/annurev-pathol-011110-130318","article-title":"The Th17 pathway and inflammatory diseases of the intestines, lungs, and skin","volume":"8","author":"Weaver","year":"2013","journal-title":"Annu Rev Pathol.: Mech Dis"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2014.00508","article-title":"Neutrophil-derived cytokines : facts beyond expression","volume":"5","author":"Tecchio","year":"2014","journal-title":"Front Immunol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.cellimm.2018.01.005","article-title":"Alveolar Macrophages","volume":"330","author":"Joshi","year":"2018","journal-title":"Cell Immunol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2019.1032","article-title":"The role of the anti-inflammatory cytokine interleukin-10 in tissue fibrosis","volume":"9","author":"Steen","year":"2020","journal-title":"Adv Wound Care"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1255354","article-title":"Macrophages: Master regulators of inflammation and fibrosis","volume":"30","author":"Wynn","year":"2010","journal-title":"Semin Liver Dis"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2005-0003OC","article-title":"Interleukin-25 and interleukin-13 production by alveolar macrophages in response to particles","volume":"33","author":"Kang","year":"2005","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046989","article-title":"Type II-Activated Murine Macrophages Produce IL-4","volume":"7","author":"la Flamme","year":"2012","journal-title":"PloS One"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2009.03240.x","article-title":"Interleukin-17 and its target genes: Mechanisms of interleukin-17 function in disease","volume":"129","author":"Onishi","year":"2010","journal-title":"Immunology"},{"key":"B54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-3024.1994.tb00297.x","article-title":"Toxocara canis-induced murine puImonary infIammation: analysis of cells and proteins in lung tissue and bronchoalveolar lavage fluid","author":"Buijs","year":"1994","journal-title":"Parasite Immunol"},{"key":"B55","doi-asserted-by":"crossref","DOI":"10.2307\/3282214","article-title":"Pulmonary granuloma formation in murine toxocariasis: transfer of granulomatous hypersensitivity using bronchoalveolar lavage cells","volume":"74","author":"Kayes","year":"1988","journal-title":"J Parasitol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903332","article-title":"Essential role of IL-17A in the formation of a mycobacterial infection-induced granuloma in the lung","volume":"184","author":"Okamoto Yoshida","year":"2010","journal-title":"J Immunol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00949","article-title":"Th17-inducing cytokines il-6 and il-23 are crucial for granuloma Formation during experimental Paracoccidioidomycosis","volume":"8","author":"Sales","year":"2017","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.864632\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T11:09:35Z","timestamp":1656500975000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.864632\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,29]]},"references-count":57,"alternative-id":["10.3389\/fimmu.2022.864632"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.864632","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,29]]},"article-number":"864632"}}