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Interleukin-4 activated macrophages mediate immunity to filarial helminth
infection by sustaining CCR3-dependent eosinophilia
#MMPMID29547639
Turner JD
; Pionnier N
; Furlong-Silva J
; Sjoberg H
; Cross S
; Halliday A
; Guimaraes AF
; Cook DAN
; Steven A
; Van Rooijen N
; Allen JE
; Jenkins SJ
; Taylor MJ
PLoS Pathog
2018[Mar]; 14
(3
): e1006949
PMID29547639
show ga
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.
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