Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory, South Africa.
National Health Laboratory Service, Johannesburg, South Africa.
Immunology. 2021 Feb;162(2):220-234. doi: 10.1111/imm.13277. Epub 2020 Oct 23.
TNF signalling through TNFRp55 and TNFRp75, and receptor shedding is important for immune activation and regulation. TNFRp75 deficiency leads to improved control of Mycobacterium tuberculosis (M. tuberculosis) infection, but the effects of early innate immune events in this process are unclear. We investigated the role of TNFRp75 on cell activation and apoptosis of alveolar macrophages and neutrophils during M. tuberculosis and M. bovis BCG infection. We found increased microbicidal activity against M. tuberculosis occurred independently of IFNy and NO generation, and displayed an inverse correlation with alveolar macrophages (AMs) apoptosis. Both M. tuberculosis and M. bovis BCG induced higher expression of MHC-II in TNFRp75 AMs; however, M bovis BCG infection did not alter AM apoptosis in the absence of TNFRp75. Pulmonary concentrations of CCL2, CCL3 and IL-1β were increased in TNFRp75 mice during M, bovis BCG infection, but had no effect on neutrophil responses. Thus, TNFRp75-dependent regulation of mycobacterial replication is virulence dependent and occurs independently of early alveolar macrophage apoptosis and neutrophil responses.
TNF 通过 TNFRp55 和 TNFRp75 的信号转导以及受体脱落对于免疫激活和调节很重要。TNFRp75 缺乏会导致对结核分枝杆菌（M. tuberculosis）感染的更好控制，但在此过程中早期先天免疫事件的影响尚不清楚。我们研究了 TNFRp75 在结核分枝杆菌和牛分枝杆菌 BCG 感染期间对肺泡巨噬细胞和中性粒细胞的细胞激活和凋亡的作用。我们发现，针对结核分枝杆菌的杀菌活性增加与 IFNy 和 NO 的产生无关，并且与肺泡巨噬细胞（AMs）凋亡呈负相关。结核分枝杆菌和牛分枝杆菌 BCG 均诱导 TNFRp75 AMs 中 MHC-II 的更高表达；然而，在没有 TNFRp75 的情况下，牛分枝杆菌 BCG 感染不会改变 AM 凋亡。在牛分枝杆菌 BCG 感染期间，TNFRp75 小鼠肺中的 CCL2、CCL3 和 IL-1β 浓度增加，但对中性粒细胞反应没有影响。因此，依赖于 TNFRp75 的分枝杆菌复制的调节与毒力有关，并且与早期肺泡巨噬细胞凋亡和中性粒细胞反应无关。
