Interleukin-4 activated macrophages mediate immunity to filarial helminth infection by sustaining CCR3-dependent eosinophilia.
PLoS Pathog
; 14(3): e1006949, 2018 03.
Article
en En
| MEDLINE
| ID: mdl-29547639
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 (MÏ) 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 MÏ populations proliferated and became alternatively-activated (AAMÏ). Filarial AAMÏ development required adaptive immunity and interleukin-4 receptor-alpha. Depletion of MÏ prior to infection suppressed eosinophilia and facilitated worm survival. Add back of filarial AAMÏ in MÏ-depleted mice recapitulated a vigorous eosinophilia. Transfer of filarial AAMÏ into Severe-Combined Immune Deficient mice mediated immunological resistance in an eosinophil-dependent manner. Exogenous IL-4 delivery recapitulated tissue AAMÏ expansions, sustained eosinophilia and mediated immunological resistance in MÏ-intact SCID mice. Co-culturing Brugia with filarial AAMÏ and/or filarial-recruited eosinophils confirmed eosinophils as the larvicidal cell type. Our data demonstrates that IL-4/IL-4Rα activated AAMÏ orchestrate eosinophil immunity to filarial tissue helminth infection.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Interleucina-4
/
Brugia Malayi
/
Eosinofilia
/
Receptores CCR3
/
Filariasis
/
Macrófagos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
PLoS Pathog
Año:
2018
Tipo del documento:
Article
País de afiliación:
Reino Unido