Local macrophage clean-up Infection, especially by helminths or bacteria, can cause tissue damage (see the Perspective by Bouchery and Harris). Minutti et al. studied mouse models of helminth infection and fibrosis. They expressed surfactant protein A (a member of the complement component C1q family) in the lung, which enhanced interleukin-4 (IL-4)-mediated proliferation and activation of alveolar macrophages. This activation accelerated helminth clearance and reduced lung injury. In the peritoneum, C1q boosted macrophage activation for liver repair after bacterial infection. By a different approach, Bosurgi et al. discovered that after wounding caused by migrating helminths in the lung or during inflammation in the gut of mice, IL-4 and IL-13 act only in the presence of apoptotic cells to promote tissue repair by local macrophages. Science, this issue p. 1076, p. 1072; see also p. 1014 Just as infection needs to be limited, so must healing responses be contained to reduce scarring and allergy. The type 2 immune response controls helminth infection and maintains tissue homeostasis but can lead to allergy and fibrosis if not adequately regulated. We have discovered local tissue-specific amplifiers of type 2–mediated macrophage activation. In the lung, surfactant protein A (SP-A) enhanced interleukin-4 (IL-4)–dependent macrophage proliferation and activation, accelerating parasite clearance and reducing pulmonary injury after infection with a lung-migrating helminth. In the peritoneal cavity and liver, C1q enhancement of type 2 macrophage activation was required for liver repair after bacterial infection, but resulted in fibrosis after peritoneal dialysis. IL-4 drives production of these structurally related defense collagens, SP-A and C1q, and the expression of their receptor, myosin 18A. These findings reveal the existence within different tissues of an amplification system needed for local type 2 responses.

中文翻译：

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IL-4Rα介导的巨噬细胞活化的局部放大器促进肺和肝的修复

局部巨噬细胞清除感染，尤其是蠕虫或细菌感染，会导致组织损伤（参见 Bouchery 和 Harris 的观点）。米努蒂等人。研究了蠕虫感染和纤维化的小鼠模型。他们在肺中表达表面活性蛋白 A（补体成分 C1q 家族的成员），从而增强白细胞介素 4 (IL-4) 介导的肺泡巨噬细胞增殖和活化。这种激活加速了蠕虫的清除并减少了肺损伤。在腹膜中，C1q 促进巨噬细胞活化，用于细菌感染后的肝脏修复。通过不同的方法，Bosurgi 等人。发现在肺部迁移蠕虫造成的伤害或小鼠肠道炎症期间，IL-4和IL-13仅在凋亡细胞存在的情况下起作用，以促进局部巨噬细胞的组织修复。科学，这个问题p。第 1076 页，第 1072; 另见第 1014 正如需要限制感染一样，必须控制愈合反应以减少疤痕和过敏。2 型免疫反应控制蠕虫感染并维持组织稳态，但如果调节不当，可能导致过敏和纤维化。我们发现了 2 型介导的巨噬细胞活化的局部组织特异性放大器。在肺中，表面活性蛋白 A (SP-A) 增强了白细胞介素 4 (IL-4) 依赖性巨噬细胞的增殖和活化，加速了寄生虫的清除并减少了肺迁移蠕虫感染后的肺损伤。在腹膜腔和肝脏中，细菌感染后肝脏修复需要 C1q 增强 2 型巨噬细胞活化，但在腹膜透析后导致纤维化。IL-4 驱动这些结构相关的防御性胶原蛋白 SP-A 和 C1q 的产生，以及它们的受体肌球蛋白 18A 的表达。这些发现揭示了局部 2 型反应所需的放大系统存在于不同组织中。