Eosinophil-Mediated Immune Control of Adult Filarial Nematode Infection Can Proceed in the Absence of IL-4 Receptor Signaling



Pionnier, Nicolas, Sjoberg, Hanna, Furlong-Silva, Julio, Marriott, Amy, Halliday, Alice, Archer, John, Steven, Andrew, Taylor, Mark J and Turner, Joseph D
(2020) Eosinophil-Mediated Immune Control of Adult Filarial Nematode Infection Can Proceed in the Absence of IL-4 Receptor Signaling. JOURNAL OF IMMUNOLOGY, 205 (3). 731 - 740.

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Abstract

Helminth infections are accompanied by eosinophilia in parasitized tissues. 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–dependent 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-4Rα–deficient (IL-4Rα−/−) mice, whereby the majority of infections do not achieve patency. An associated residual eosinophilia was apparent in infected IL-4Rα−/− mice. By treating IL-4Rα−/− mice serially with anti-CCR3 Ab or introducing a compound deficiency in CCR3 within IL-4Rα−/− 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–dependent immune mechanisms. We investigated additional cytokine signals involved in residual eosinophilia in the absence IL-4Rα signaling and defined that IL-4Rα−/−/IL-5−/− double-knockout mice displayed significant eosinophil deficiency compared with IL-4Rα−/− mice and were susceptible to chronic fecund adult filarial infections. Contrastingly, there was no evidence that either IL-4R–dependent or IL-4R–independent/CCR3/IL-5–dependent 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–independent/IL-5– and CCR3-dependent pathways are sufficient to control filarial adult infection via an eosinophil-dependent effector response prior to patency.

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 10 Sep 2020 12:10
Last Modified: 19 Jan 2021 03:10
DOI: 10.4049/jimmunol.1901244
Open Access URL: https://doi.org/10.4049/jimmunol.1901244
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3100667