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