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髓系细胞募集与局部增殖区分了对丝虫感染的易感性和抗性。

Myeloid cell recruitment versus local proliferation differentiates susceptibility from resistance to filarial infection.

机构信息

Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.

Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, Faculty of Biology, Medicine & Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom.

出版信息

Elife. 2018 Jan 4;7:e30947. doi: 10.7554/eLife.30947.

Abstract

Both T2-dependent helminth killing and suppression of the T2 effector response have been attributed to macrophages (MΦ) activated by IL-4 (M(IL-4)). To investigate how M(IL-4) contribute to diverse infection outcomes, the MΦ compartment of susceptible BALB/c mice and more resistant C57BL/6 mice was profiled during infection of the pleural cavity with the filarial nematode, C57BL/6 mice exhibited a profoundly expanded resident MΦ (resMΦ) population, which was gradually replenished from the bone marrow in an age-dependent manner. Infection status did not alter the bone-marrow derived contribution to the resMΦ population, confirming local proliferation as the driver of resMΦ expansion. Significantly less resMΦ expansion was observed in the susceptible BALB/c strain, which instead exhibited an influx of monocytes that assumed an immunosuppressive PD-L2 phenotype. Inhibition of monocyte recruitment enhanced nematode killing. Thus, the balance of monocytic vs. resident M(IL-4) numbers varies between inbred mouse strains and impacts infection outcome.

摘要

T2 依赖性寄生虫杀伤和 T2 效应器反应的抑制都归因于 IL-4(M(IL-4))激活的巨噬细胞(MΦ)。为了研究 M(IL-4)如何促成不同的感染结果,在胸腔内感染丝虫时,对易感 BALB/c 小鼠和更具抗性的 C57BL/6 小鼠的 MΦ 区室进行了分析。C57BL/6 小鼠表现出明显扩大的常驻 MΦ(resMΦ)群体,该群体以年龄依赖性的方式从骨髓中逐渐补充。感染状态并未改变骨髓对 resMΦ 群体的贡献,这证实了局部增殖是 resMΦ 扩张的驱动因素。在易感的 BALB/c 品系中观察到的 resMΦ 扩张明显较少,而是观察到单核细胞的流入,这些单核细胞表现出免疫抑制 PD-L2 表型。抑制单核细胞募集可增强寄生虫杀伤。因此,固有小鼠品系之间单核细胞与常驻 M(IL-4)数量的平衡不同,这会影响感染结果。

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