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- Title
Interleukin-4 activated macrophages mediate immunity to filarial helminth infection by sustaining CCR3-dependent eosinophilia.
- Authors
Turner, Joseph D.; Pionnier, Nicolas; Furlong-Silva, Julio; Sjoberg, Hanna; Cross, Stephen; Halliday, Alice; Guimaraes, Ana F.; Cook, Darren A. N.; Steven, Andrew; Van Rooijen, Nico; Allen, Judith E.; Jenkins, Stephen J.; Taylor, Mark J.
- 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.
- Subjects
INTERLEUKIN-4; HELMINTHIASIS; MACROPHAGES; IMMUNOPATHOLOGY; CHEMOKINE receptors; EOSINOPHILIA
- Publication
PLoS Pathogens, 2018, Vol 14, Issue 3, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1006949