{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:30:12Z","timestamp":1790746212789,"version":"4.1.0"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T00:00:00Z","timestamp":1664236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"Lymphatic filariasis and onchocerciasis are major neglected tropical diseases affecting over 90 million people worldwide with painful and profoundly disfiguring pathologies (such as lymphoedema or blindness). Type 2 inflammation is a hallmark of filarial nematode tissue infection and is implicated both in eosinophil dependent immunity and lymphatic or ocular immunopathologies. Type-2 innate lymphoid cells (ILC2) are known to play an important role in the initiation of type 2 inflammation in helminth infection. We therefore tracked comparative IL-12R\u03b22+<\/jats:sup>ILC1, ST2+<\/jats:sup>ILC2 and NKp46+<\/jats:sup>natural killer (NK) innate lymphoid cell population expansions duringBrugia malayi<\/jats:italic>experimental peritoneal filarial infections using either immunocompetent or immunodeficient mice. In immunocompetent BALB\/c animals, NKp46+<\/jats:sup>NK cells rapidly expanded representing over 90% of the ILC population in the first week of infection, whereas, surprisingly, ST2+<\/jats:sup>ILC2 failed to expand. NKp46+<\/jats:sup>NK cell expansions were confirmed in RAG2 deficient mice lacking adaptive immunity. Ablation of the NKp46+<\/jats:sup>NK cell compartment in RAG2 common gamma chain (gc) mice led to increased susceptibility to chronic adultB. malayi<\/jats:italic>infection. This data was recapitulated using anOnchocerca ochengi<\/jats:italic>male worm peritoneal implant model. When NKp46+<\/jats:sup>NK cells were depleted in RAG2 deficient mice using anti-NKp46 or asialo GM1 antibody injections over the first five weeks ofB. malayi<\/jats:italic>infection, susceptibility to adultB. malayi<\/jats:italic>infection was significantly increased by 2-3 fold with concomitant impairment in eosinophil or neutrophil recruitments. Finally, we demonstrate that in RAG2 deficient mice, drug clearance of a primary adultB. malayi<\/jats:italic>infection followed by challenge infection leads to resistance against early larvalB. malayi<\/jats:italic>establishment. This innate resistance is associated with bolstered NK and eosinophils whereby NKp46+<\/jats:sup>NK cells express markers of memory-like\/enhanced activation (increased expression of interferon gamma and Ly6C). Our data promotes a novel functional role for NKp46+<\/jats:sup>NK cells in immunoprotection against experimental primary and secondary filarial infection which can proceed in the absence of adaptive immune regulation.<\/jats:p>","DOI":"10.3389\/fimmu.2022.969340","type":"journal-article","created":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T06:57:10Z","timestamp":1664261830000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["NKp46+ natural killer cells develop an activated\/memory-like phenotype and contribute to innate immunity against experimental filarial infection"],"prefix":"10.3389","volume":"13","author":[{"given":"Nicolas","family":"Pionnier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Furlong-Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano A. 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