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

嗜酸性粒细胞是对组织蠕虫免疫的效应子，但也可引起过敏性免疫病理。感染期间非粘膜组织中嗜酸性粒细胞增多的机制仍未解决。在这里，我们使用BALB / c小鼠腹膜内马来酸布鲁氏菌鉴定了嗜酸性粒细胞抗蠕虫免疫中组织巨噬细胞（Mϕ）的关键功能丝虫感染模型。经由CC基序趋化因子受体（CCR）3的嗜酸性粒细胞增多是免疫所必需的，因为CCR3和嗜酸性粒细胞损害使小鼠易患慢性丝状感染。感染后，腹膜M +群体增生并被交替激活（AAM +）。丝状AAMϕ的发育需要适应性免疫和白介素4受体-α。感染前M 3的消耗抑制了嗜酸性粒细胞增多，并促进了蠕虫的存活。在M +耗尽的小鼠中添加丝状AAM 3，概括了剧烈的嗜酸性粒细胞增多。将丝状AAM 3转移至严重结合免疫缺陷小鼠中，以嗜酸性粒细胞依赖性方式介导免疫抵抗。外源性IL-4递送在完整的Mϕ完整的SCID小鼠体内概括了组织AAMϕ的扩增，持续的嗜酸性粒细胞增多和介导的免疫抗性。共同培养带有丝状AAM +和/或丝状嗜酸性粒细胞的Brugia证实嗜酸性粒细胞为幼虫细胞类型。我们的数据表明，IL-4 /IL-4Rα激活了AAMϕ编排对丝状组织蠕虫感染的嗜酸性粒细胞免疫力。