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

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 (M?) 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 M? populations proliferated and became alternatively-activated (AAM?). Filarial AAM? development required adaptive immunity and interleukin-4 receptor-alpha. Depletion of M? prior to infection suppressed eosinophilia and facilitated worm survival. Add back of filarial AAM? in M?-depleted mice recapitulated a vigorous eosinophilia. Transfer of filarial AAM? into Severe-Combined Immune Deficient mice mediated immunological resistance in an eosinophil-dependent manner. Exogenous IL-4 delivery recapitulated tissue AAM? expansions, sustained eosinophilia and mediated immunological resistance in M?-intact SCID mice. Co-culturing Brugia with filarial AAM? and/or filarial-recruited eosinophils confirmed eosinophils as the larvicidal cell type. Our data demonstrates that IL-4/IL-4R? activated AAM? orchestrate eosinophil immunity to filarial tissue helminth infection.

SUBMITTER: Turner JD 

PROVIDER: S-EPMC5874077 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature