Efferocytosis of Apoptotic Neutrophils Enhances Control of Mycobacterium tuberculosis in HIV-Coinfected Macrophages in a Myeloperoxidase-Dependent Manner
Efferocytosis of Apoptotic Neutrophils Enhances Control of Mycobacterium tuberculosis in HIV-Coinfected Macrophages in a Myeloperoxidase-Dependent Manner
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DOI：
10.1159/000500861
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发表时间：
2020-05-01
影响因子：
5.3
通讯作者：
Blomgran, Robert
中科院分区：
文献类型：
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作者：
Andersson, Anna-Maria;Larsson, Marie;Blomgran, Robert
结核病仍然是一个巨大的威胁，2017年有160万人死亡，其中包括30万艾滋病毒感染者。在艾滋病毒合并感染期间，发生活动性疾病的风险大大增加。肺泡巨噬细胞是第一个遇到病原体结核分枝杆菌的免疫细胞，但在肉芽肿形成期间，其他细胞被招募以对抗细菌。在此，我们研究了M.结核病和HIV共感染的巨噬细胞在人类体外系统中的作用。我们发现凋亡的中性粒细胞增强了M.结核病在单一和HIV共感染的巨噬细胞，这是依赖于髓过氧化物酶（MPO）和活性氧在自噬独立的方式。我们发现MPO在凋亡的中性粒细胞中保持活性，并且可以被感染的巨噬细胞利用。此外，MPO抑制消除了M.结核病的增长所造成的凋亡中性粒细胞。因此，凋亡中性粒细胞的抗分枝杆菌成分可以增加M.结核病/艾滋病毒合并感染。因此，先天免疫细胞之间的这种合作可能是一种补偿针对M.在同时感染艾滋病病毒期间出现的结核病。
Tuberculosis remains a big threat, with 1.6 million deaths in 2017, including 0.3 million deaths among patients with HIV. The risk of developing active disease increases considerably during an HIV coinfection. Alveolar macrophages are the first immune cells to encounter the causative agent Mycobacterium tuberculosis, but during the granuloma formation other cells are recruited in order to combat the bacteria. Here, we have investigated the effect of efferocytosis of apoptotic neutrophils by M. tuberculosis and HIV-coinfected macrophages in a human in vitro system. We found that the apo-ptotic neutrophils enhanced the control of M. tuberculosis in single and HIV-coinfected macrophages, and that this was dependent on myeloperoxidase (MPO) and reactive oxygen species in an autophagy-independent manner. We show that MPO remains active in the apoptotic neutrophils and can be harnessed by infected macrophages. In addition, MPO inhibition removed the suppression in M. tuberculosis growth caused by the apoptotic neutrophils. Antimycobacterial components from apoptotic neutrophils could thus increase the microbicidal activity of macrophages during an M. tuberculosis/HIV coinfection. This cooperation between innate immune cells could thereby be a way to compensate for the impaired adaptive immunity against M. tuberculosis seen during a concurrent HIV infection.