Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, WC1E 7HT, London, UK.
Cell Microbiol. 2012 Jul;14(7):1109-21. doi: 10.1111/j.1462-5822.2012.01783.x. Epub 2012 Apr 13.
Neutrophils enter sites of infection, where they can eliminate pathogenic bacteria in an oxidative manner. Despite their predominance in active tuberculosis lesions, the function of neutrophils in this important human infection is still highly controversial. We observed that virulent Mycobacterium tuberculosis survived inside human neutrophils despite prompt activation of these defence cells' microbicidal effectors. Survival of M. tuberculosis was accompanied by necrotic cell death of infected neutrophils. Necrotic cell death entirely depended on radical oxygen species production since chronic granulomatous disease neutrophils were protected from M. tuberculosis-triggered necrosis. More, importantly, the M. tuberculosis ΔRD1 mutant failed to induce neutrophil necrosis rendering this strain susceptible to radical oxygen species-mediated killing. We conclude that this virulence function is instrumental for M. tuberculosis to escape killing by neutrophils and contributes to pathogenesis in tuberculosis.
中性粒细胞进入感染部位，以氧化方式消除致病细菌。尽管中性粒细胞在活动性肺结核病变中占优势，但它们在这种重要的人类感染中的功能仍存在很大争议。我们观察到，尽管这些防御细胞的杀菌效应器迅速被激活，但毒力结核分枝杆菌仍能在人中性粒细胞内存活。结核分枝杆菌的存活伴随着受感染中性粒细胞的坏死性细胞死亡。坏死性细胞死亡完全依赖于活性氧的产生，因为慢性肉芽肿病中性粒细胞免受结核分枝杆菌引发的坏死。更重要的是，结核分枝杆菌 ΔRD1 突变体不能诱导中性粒细胞坏死，使该菌株易受活性氧介导的杀伤。我们的结论是，这种毒力功能对于结核分枝杆菌逃避中性粒细胞的杀伤至关重要，并有助于结核病的发病机制。
