澳大利亚沃尔特和伊丽莎霍尔医学研究所Marc Pellegrini研究团队发现巨噬细胞和中性粒细胞死亡程序分别赋予抵抗结核病 (TB)的能力。2021年7月12日国际知名学术期刊《免疫》发表了这一成果。

他们定义了死亡受体介导和 BCL-2 调节的细胞凋亡途径在介导结核病保护中的关键体内功能，通过消除不同受感染巨噬细胞和中性粒细胞群并引发 T 细胞反应。他们进一步表明，细胞凋亡途径可以通过临床阶段的化合物进行治疗，这些化合物拮抗细胞凋亡抑制剂 (IAP) 蛋白以促进小鼠结核分枝杆菌的清除。

这些发现表明，结核分枝杆菌对细胞凋亡的任何抑制在体内都是不完全的，这促进了人们对宿主对TB 保护反应的理解，并揭示了可作为治疗疾病的目标的宿主途径。

研究人员表示，细胞凋亡可以通过直接杀死微生物并消除其复制生态位来有效抵御细胞内病原体。然而，尽管缺乏体内证据，据报道，结核分枝杆菌在体外限制巨噬细胞凋亡途径的能力导致细胞凋亡，被认为是结核病的宿主保护过程。

附：英文原文

Title: Macrophage and neutrophil death programs differentially confer resistance to tuberculosis

Author: Michael Dominic Stutz, Cody Charles Allison, Samar Ojaimi, Simon Peter Preston, Marcel Doerflinger, Philip Arandjelovic, Lachlan Whitehead, Stefanie M. Bader, Daniel Batey, Marie-Liesse Asselin-Labat, Marco J. Herold, Andreas Strasser, Nicholas P. West, Marc Pellegrini

Issue&Volume: 2021-07-12

Abstract: Apoptosis can potently defend against intracellular pathogens by directly killingmicrobes and eliminating their replicative niche. However, the reported ability ofMycobacterium tuberculosis to restrict apoptotic pathways in macrophages in vitro has led to apoptosis being dismissed as a host-protective process in tuberculosisdespite a lack of in vivo evidence. Here we define crucial in vivo functions of the death receptor-mediated and BCL-2-regulated apoptosis pathways inmediating protection against tuberculosis by eliminating distinct populations of infectedmacrophages and neutrophils and priming T cell responses. We further show that apoptoticpathways can be targeted therapeutically with clinical-stage compounds that antagonizeinhibitor of apoptosis (IAP) proteins to promote clearance of M. tuberculosis in mice. These findings reveal that any inhibition of apoptosis by M. tuberculosis is incomplete in vivo, advancing our understanding of host-protective responses to tuberculosis (TB) andrevealing host pathways that may be targetable for treatment of disease.

DOI: 10.1016/j.immuni.2021.06.009

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00253-3