Interleukin-4 activated macrophages mediate immunity to filarial helminth infection by sustaining CCR3-dependent eosinophilia



Turner, Joseph D, Pionnier, Nicolas, Furlong-Silva, Julio, Sjoberg, Hanna, Cross, Stephen, Halliday, Alice, Guimaraes, Ana F, Cook, Darren AN, Steven, Andrew, Van Rooijen, Nico
et al (show 3 more authors) (2018) Interleukin-4 activated macrophages mediate immunity to filarial helminth infection by sustaining CCR3-dependent eosinophilia. PLOS PATHOGENS, 14 (3). e1006949-.

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Abstract

Eosinophils are effectors in immunity to tissue helminths but also induce allergic immunopathology. Mechanisms of eosinophilia in non-mucosal tissues during infection remain unresolved. Here we identify a pivotal function of tissue macrophages (Mϕ) in eosinophil anti-helminth immunity using a BALB/c mouse intra-peritoneal Brugia malayi filarial infection model. Eosinophilia, via C-C motif chemokine receptor (CCR)3, was necessary for immunity as CCR3 and eosinophil impairments rendered mice susceptible to chronic filarial infection. Post-infection, peritoneal Mϕ populations proliferated and became alternatively-activated (AAMϕ). Filarial AAMϕ development required adaptive immunity and interleukin-4 receptor-alpha. Depletion of Mϕ prior to infection suppressed eosinophilia and facilitated worm survival. Add back of filarial AAMϕ in Mϕ-depleted mice recapitulated a vigorous eosinophilia. Transfer of filarial AAMϕ into Severe-Combined Immune Deficient mice mediated immunological resistance in an eosinophil-dependent manner. Exogenous IL-4 delivery recapitulated tissue AAMϕ expansions, sustained eosinophilia and mediated immunological resistance in Mϕ-intact SCID mice. Co-culturing Brugia with filarial AAMϕ and/or filarial-recruited eosinophils confirmed eosinophils as the larvicidal cell type. Our data demonstrates that IL-4/IL-4Rα activated AAMϕ orchestrate eosinophil immunity to filarial tissue helminth infection.

Item Type: Article
Uncontrolled Keywords: Macrophages, Animals, Mice, Inbred BALB C, Mice, Mice, SCID, Brugia malayi, Filariasis, Eosinophilia, Antineoplastic Agents, Interleukin-4, Cytokines, Female, Male, Receptors, CCR3
Depositing User: Symplectic Admin
Date Deposited: 15 May 2019 09:40
Last Modified: 19 Jan 2023 00:45
DOI: 10.1371/journal.ppat.1006949
Open Access URL: https://doi.org/10.1371/journal.ppat.1006949
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3041429