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

Research output: Contribution to journalArticle

  • External authors:
  • Joseph D. Turner
  • Nicolas Pionnier
  • Julio Furlong-Silva
  • Hanna Sjoberg
  • Stephen Cross
  • Alice Halliday
  • Ana Guimaraes
  • Darren Cook
  • Andrew Steven
  • Nico Van Rooijen
  • Stephen Jenkins
  • Mark J. Taylor

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 filarialrecruited eosinophils confirmed eosinophils as the larvicidal cell type. Our data demonstrates that IL-4/IL-4RD activated AAMϕ orchestrate eosinophil immunity to filarial tissue helminth infection.

Bibliographical metadata

Original languageEnglish
JournalPL o S Pathogens
Early online date16 Mar 2018
DOIs
StatePublished - 2018