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Eosinophils are effectors of immunity to tissue helminths. We previously reported that in the context of experimental filarial nematode infection, optimum tissue eosinophil recruitment was coordinated by local macrophage populations following IL-4R\u2013dependent in situ proliferation and alternative activation. However, in the current study, we identify that control of chronic adult filarial worm infection is evident in IL-4R\u03b1\u2013deficient (IL-4R\u03b1\u2212\/\u2212) mice, whereby the majority of infections do not achieve patency. An associated residual eosinophilia was apparent in infected IL-4R\u03b1\u2212\/\u2212 mice. By treating IL-4R\u03b1\u2212\/\u2212 mice serially with anti-CCR3 Ab or introducing a compound deficiency in CCR3 within IL-4R\u03b1\u2212\/\u2212 mice, residual eosinophilia was ablated, and susceptibility to chronic adult Brugia malayi infection was established, promoting a functional role for CCR3-dependent eosinophil influx in immune control in the absence of IL-4\/IL-13\u2013dependent immune mechanisms. We investigated additional cytokine signals involved in residual eosinophilia in the absence IL-4R\u03b1 signaling and defined that IL-4R\u03b1\u2212\/\u2212\/IL-5\u2212\/\u2212 double-knockout mice displayed significant eosinophil deficiency compared with IL-4R\u03b1\u2212\/\u2212 mice and were susceptible to chronic fecund adult filarial infections. Contrastingly, there was no evidence that either IL-4R\u2013dependent or IL-4R\u2013independent\/CCR3\/IL-5\u2013dependent immunity influenced B. malayi microfilarial loads in the blood. Our data demonstrate multiplicity of Th2-cytokine control of eosinophil tissue recruitment during chronic filarial infection and that IL-4R\u2013independent\/IL-5\u2013 and CCR3-dependent pathways are sufficient to control filarial adult infection via an eosinophil-dependent effector response prior to patency.<\/jats:p>","DOI":"10.4049\/jimmunol.1901244","type":"journal-article","created":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T19:55:13Z","timestamp":1592855713000},"page":"731-740","source":"Crossref","is-referenced-by-count":22,"title":["Eosinophil-Mediated Immune Control of Adult Filarial Nematode Infection Can Proceed in the Absence of IL-4 Receptor Signaling"],"prefix":"10.1093","volume":"205","author":[{"given":"Nicolas","family":"Pionnier","sequence":"first","affiliation":[{"name":"Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine , Liverpool L3 5QA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1948-6779","authenticated-orcid":false,"given":"Hanna","family":"Sjoberg","sequence":"additional","affiliation":[{"name":"Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine , Liverpool L3 5QA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3313-8650","authenticated-orcid":false,"given":"Julio","family":"Furlong-Silva","sequence":"additional","affiliation":[{"name":"Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine , Liverpool L3 5QA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Marriott","sequence":"additional","affiliation":[{"name":"Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine , Liverpool L3 5QA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Halliday","sequence":"additional","affiliation":[{"name":"Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine , Liverpool L3 5QA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5160-7185","authenticated-orcid":false,"given":"John","family":"Archer","sequence":"additional","affiliation":[{"name":"Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine , Liverpool L3 5QA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6395-562X","authenticated-orcid":false,"given":"Andrew","family":"Steven","sequence":"additional","affiliation":[{"name":"Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine , Liverpool L3 5QA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J","family":"Taylor","sequence":"additional","affiliation":[{"name":"Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine , Liverpool L3 5QA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2185-5476","authenticated-orcid":false,"given":"Joseph D","family":"Turner","sequence":"additional","affiliation":[{"name":"Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine , Liverpool L3 5QA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,8,1]]},"reference":[{"key":"2025030417504444200_r1","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.2174\/092986712799828337","article-title":"Granulocytes in helminth infection -- who is calling the shots?","volume":"19","author":"Makepeace","year":"2012","journal-title":"Curr. 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