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

Pionnier, Nicolas ORCID: https://orcid.org/0000-0002-2379-4945, Sjoberg, Hanna, Furlong-Silva, Julio, Marriott, Amy, Halliday, Alice, Archer, John, Steven, Andrew, Taylor, Mark ORCID: https://orcid.org/0000-0003-3396-9275 and Turner, Joseph ORCID: https://orcid.org/0000-0002-2185-5476 (2020) 'Eosinophil-Mediated Immune Control of Adult Filarial Nematode Infection Can Proceed in the Absence of IL-4 Receptor Signaling'. The Journal of Immunology, Vol 205, Issue 3, pp. 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-4Ra–deficient (IL-4Ra2/2) mice, whereby the majority of infections do not achieve patency. An associated residual eosinophilia was apparent in infected IL-4Ra2/2 mice. By treating IL-4Ra2/2 mice serially with anti-CCR3 Ab or introducing a compound deficiency in CCR3 within IL-4Ra2/2 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/IL13–dependent immune mechanisms. We investigated additional cytokine signals involved in residual eosinophilia in the absence IL-4Ra signaling and defined that IL-4Ra2/2/IL-52/2 double-knockout mice displayed significant eosinophil deficiency compared with IL-4Ra2/2 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
Subjects:	WC Communicable Diseases > Tropical and Parasitic Diseases > WC 850 Nematode infections (General) WC Communicable Diseases > Tropical and Parasitic Diseases > WC 880 Filariasis and related conditions (General) WH Hemic and Lymphatic Systems > Hematologic Diseases. Immunologic Factors. Blood Banks > WH 200 Leukocytes. Leukocyte disorders (General)
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.4049/jimmunol.1901244
Depositing User:	Cathy Waldron
Date Deposited:	06 Jul 2020 11:07
Last Modified:	14 Jun 2022 09:34
URI:	https://archive.lstmed.ac.uk/id/eprint/14945

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