T lymphocyte Biology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA.
Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA 41810-710, Brazil; Bahiana School of Medicine and Public Health (EBMSP), Salvador, BA 40296, Brazil.
Cell Rep. 2022 May 31;39(9):110896. doi: 10.1016/j.celrep.2022.110896.
HIV/Mycobacterium tuberculosis (Mtb) co-infected individuals have an increased risk of tuberculosis prior to loss of peripheral CD4 T cells, raising the possibility that HIV co-infection leads to CD4 T cell depletion in lung tissue before it is evident in blood. Here, we use rhesus macaques to study the early effects of simian immunodeficiency virus (SIV) co-infection on pulmonary granulomas. Two weeks after SIV inoculation of Mtb-infected macaques, Mtb-specific CD4 T cells are dramatically depleted from granulomas, before CD4 T cell loss in blood, airways, and lymph nodes, or increases in bacterial loads or radiographic evidence of disease. Spatially, CD4 T cells are preferentially depleted from the granuloma core and cuff relative to B cell-rich regions. Moreover, live imaging of granuloma explants show that intralesional CD4 T cell motility is reduced after SIV co-infection. Thus, granuloma CD4 T cells may be decimated before many co-infected individuals experience the first symptoms of acute HIV infection.
HIV/结核分枝杆菌（Mtb）合并感染个体在丧失外周血 CD4 T 细胞之前，患结核病的风险增加，这提示 HIV 合并感染可能导致肺部组织中 CD4 T 细胞耗竭，而外周血尚未出现明显变化。在这里，我们使用恒河猴来研究猴免疫缺陷病毒（SIV）合并感染对肺部肉芽肿的早期影响。在 Mtb 感染的恒河猴接种 SIV 两周后，Mtb 特异性 CD4 T 细胞从肉芽肿中大量耗竭，随后才出现外周血、气道和淋巴结中 CD4 T 细胞丢失，细菌负荷增加或影像学疾病证据。从空间上看，CD4 T 细胞优先从肉芽肿核心和袖套区域耗竭，而不是富含 B 细胞的区域。此外，对肉芽肿外植体的活体成像显示，SIV 合并感染后，瘤内 CD4 T 细胞的运动性降低。因此，在许多合并感染个体出现急性 HIV 感染的第一个症状之前，肉芽肿内的 CD4 T 细胞可能已大量减少。
