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

被引：44

作者：

Turner, Joseph D. ^{[1
]}

Pionnier, Nicolas ^{[1
]}

Furlong-Silva, Julio ^{[1
]}

Sjoberg, Hanna ^{[1
]}

Cross, Stephen ^{[1
]}

Halliday, Alice ^{[1
]}

Guimaraes, Ana F. ^{[1
]}

Cook, Darren A. N. ^{[1
]}

Steven, Andrew ^{[1
]}

Van Rooijen, Nico ^{[2
]}

Allen, Judith E. ^{[3
]}

Jenkins, Stephen J. ^{[4
]}

Taylor, Mark J. ^{[1
]}

机构：

[1] Univ Liverpool Liverpool Sch Trop Med, Res Ctr Drugs & Diagnost, Liverpool, Merseyside, England

[2] Vrije Univ Amsterdam, Dept Mol Cell Biol & Immunol, Med Ctr, Amsterdam, Netherlands

[3] Univ Manchester, Fac Biol Med & Hlth, Manchester, Lancs, England

[4] Univ Edinburgh, MRC Ctr Inflammat Res, Edinburgh, Midlothian, Scotland

来源：

PLOS PATHOGENS | 2018年 / 14卷 / 03期

基金：

英国医学研究理事会;

关键词：

MAJOR BASIC-PROTEIN; INNATE LYMPHOID TYPE-2; IN-VIVO; STRONGYLOIDES-STERCORALIS; PROTECTIVE IMMUNITY; CELLULAR-RESPONSES; CELLS; INFLAMMATION; MICE; PROLIFERATION;

D O I：

10.1371/journal.ppat.1006949

中图分类号：

Q93 [微生物学];

学科分类号：

071005 [微生物学];

摘要：

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

引用

页数：20

共 55 条

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Memory TH2 cells induce alternatively activated macrophages to mediate protection against nematode parasites [J].