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PLoS Pathog. 2018 Mar 16;14(3):e1006949. doi: 10.1371/journal.ppat.1006949. eCollection 2018 Mar.

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

Author information

1
Research Centre for Drugs & Diagnostics, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
2
VU University Medical Center, Department of Molecular Cell Biology and Immunology, Amsterdam, Netherlands.
3
Faculty of Biology, Medicine & Health, University of Manchester, Manchester, United Kingdom.
4
MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom.

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.

PMID:
29547639
PMCID:
PMC5874077
DOI:
10.1371/journal.ppat.1006949
[Indexed for MEDLINE]
Free PMC Article

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