Section for Microbiology and Immunology, The Gade Institute, University of Bergen, Laboratory Building, 5th Floor, Haukeland University Hospital, N-5021 Bergen, Norway.
Infect Immun. 2010 Sep;78(9):4022-32. doi: 10.1128/IAI.00106-10. Epub 2010 Jul 12.
Coinfection with human immunodeficiency virus type 1 (HIV-1) and opportunistic mycobacteria, especially Mycobacterium tuberculosis, is a cause of high morbidity and mortality worldwide. Both mycobacteria and HIV-1 may infect macrophages, and thus, coinfection may generate conditions that reciprocally influence the intracellular replication of the pathogens. Elucidation of the interaction between HIV-1 and mycobacteria in their common target cell is important for understanding pathogenesis in coinfected individuals. In this study, we investigated the effects of in vitro HIV-1 infection on the growth of M. tuberculosis, M. avium, and M. paratuberculosis in human peripheral blood monocyte-derived macrophages. Interestingly, HIV-1 infection induced a greater bacterial burden in coinfected cell cultures for all of the mycobacterial species tested and specifically induced accelerated growth of M. tuberculosis with a reduced mean generation time. The interaction of HIV-1 and M. tuberculosis was especially detrimental to the host cell, causing a significant synergistic reduction in macrophage viability. Also, in M. tuberculosis/HIV-1-coinfected cultures, increased levels of interleukin-1beta (IL-1beta), IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor were observed and viral replication was enhanced. Overall, the present data suggest that HIV-1 infection of macrophages may impair their ability to contain mycobacterial growth. Furthermore, coinfection with HIV-1 and M. tuberculosis seems to give rise to synergistic effects at the cellular level that mutually enhance the replication of both pathogens. This may, in part, contribute to the increased morbidity and mortality seen in coinfected individuals.
人免疫缺陷病毒 1 型（HIV-1）与机会性分枝杆菌（尤其是结核分枝杆菌）的合并感染是全球高发病率和高死亡率的一个原因。分枝杆菌和 HIV-1 均可感染巨噬细胞，因此合并感染可能会产生相互影响病原体细胞内复制的条件。阐明 HIV-1 和分枝杆菌在其共同靶细胞中的相互作用对于理解合并感染者的发病机制非常重要。在本研究中，我们研究了体外 HIV-1 感染对人外周血单核细胞衍生巨噬细胞中结核分枝杆菌、鸟分枝杆菌和牛分枝杆菌生长的影响。有趣的是，HIV-1 感染诱导所有测试的分枝杆菌物种在合并感染细胞培养物中的细菌负荷增加，并且特异性地诱导结核分枝杆菌的生长加速，平均代时缩短。HIV-1 和结核分枝杆菌的相互作用对宿主细胞特别有害，导致巨噬细胞活力显著协同降低。此外，在结核分枝杆菌/HIV-1 合并感染培养物中，观察到白细胞介素-1β（IL-1β）、IL-6、IL-8 和粒细胞-巨噬细胞集落刺激因子水平升高，病毒复制增强。总体而言，目前的数据表明，巨噬细胞中的 HIV-1 感染可能会损害其控制分枝杆菌生长的能力。此外，HIV-1 和结核分枝杆菌的合并感染似乎会在细胞水平上产生协同作用，相互增强两种病原体的复制。这可能部分导致合并感染者发病率和死亡率的增加。
