Pionnier, Nicolas, Furlong-Silva, Julio, Colombo, Stefano AP, Marriott, Amy EE 
ORCID: 0000-0002-4806-9539, Chunda, Valerine CC, Ndzeshang, Bertrand LL, Sjoberg, Hanna, Archer, John, Steven, Andrew, Wanji, Samuel et al (show 2 more authors)
(2022)
NKp46<SUP>+</SUP> natural killer cells develop an activated/memory-like phenotype and contribute to innate immunity against experimental filarial infection.
FRONTIERS IN IMMUNOLOGY, 13.
969340-.
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-12Rβ2<sup>+</sup> ILC1, ST2<sup>+</sup> ILC2 and NKp46<sup>+</sup> natural killer (NK) innate lymphoid cell population expansions during <i>Brugia malayi</i> experimental peritoneal filarial infections using either immunocompetent or immunodeficient mice. In immunocompetent BALB/c animals, NKp46<sup>+</sup> NK cells rapidly expanded representing over 90% of the ILC population in the first week of infection, whereas, surprisingly, ST2<sup>+</sup> ILC2 failed to expand. NKp46<sup>+</sup> NK cell expansions were confirmed in RAG2 deficient mice lacking adaptive immunity. Ablation of the NKp46<sup>+</sup> NK cell compartment in RAG2 common gamma chain (gc) mice led to increased susceptibility to chronic adult <i>B. malayi</i> infection. This data was recapitulated using an <i>Onchocerca ochengi</i> male worm peritoneal implant model. When NKp46<sup>+</sup> NK cells were depleted in RAG2 deficient mice using anti-NKp46 or asialo GM1 antibody injections over the first five weeks of <i>B. malayi</i> infection, susceptibility to adult <i>B. malayi</i> 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 adult <i>B. malayi</i> infection followed by challenge infection leads to resistance against early larval <i>B. malayi</i> establishment. This innate resistance is associated with bolstered NK and eosinophils whereby NKp46<sup>+</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<sup>+</sup> NK cells in immunoprotection against experimental primary and secondary filarial infection which can proceed in the absence of adaptive immune regulation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Brugia malayi, eosinophils, innate lymphoid cells (ILC), lymphatic filariasis, natural killer cells (NK cells), neutrophils, Rag2 knockout (KO) mouse |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences Faculty of Health and Life Sciences > Tech, Infrastructure and Environmental Directorate |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 09 Apr 2024 09:24 |
| Last Modified: | 09 Apr 2024 13:36 |
| DOI: | 10.3389/fimmu.2022.969340 |
| Open Access URL: | https://doi.org/10.3389/fimmu.2022.969340 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3180181 |
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