Center for Basic and Applied Research (CIBA), National University of the Northwest of the Province of Buenos Aires (UNNOBA), B6000DNE, Buenos Aires, Argentina.
Center for Research and Transfers of the Northwest of the Province of Buenos Aires (CIT NOBA), UNNOBA-National University of San Antonio de Areco (UNSAdA) - National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina.
J Leukoc Biol. 2021 Jan;109(1):257-273. doi: 10.1002/JLB.4MA0820-655RR. Epub 2020 Sep 29.
Tuberculosis dates back to ancient times but it is not a problem of the past. Each year, millions of people die from tuberculosis. After inhalation of infectious droplet nuclei, Mycobacterium tuberculosis reaches the lungs where it can manipulate the immune system and survive within host macrophages, establishing a persistent infection. The signaling lymphocytic activation molecule family member 1 (SLAMF1) is a self-ligand receptor that can internalize gram-negative bacteria and regulate macrophages' phagosomal functions. In tuberculosis, SLAMF1 promotes Th1-protective responses. In this work, we studied the role of SLAMF1 on macrophages' functions during M. tuberculosis infection. Our results showed that both M. tuberculosis and IFN-γ stimulation induce SLAMF1 expression in macrophages from healthy donor and Tohoku Hospital Pediatrcs-1 cells. Costimulation through SLAMF1 with an agonistic antibody resulted in an enhanced internalization of M. tuberculosis by macrophages. Interestingly, we found that SLAMF1 interacts with M. tuberculosis and colocalizes with the bacteria and with early and late endosomes/lysosomes markers (EEA1 and LAMP2), suggesting that SLAMF1 recognize M. tuberculosis and participate in the endolysosomal maturation process. Notably, increased levels of SLAMF1 were detected in CD14 cells from pleural effusions of tuberculosis patients, indicating that SLAMF1 might have an active function at the site of infection. Taken together, our results provide evidence that SLAMF1 improves the uptake of M. tuberculosis by human monocyte-derived macrophages.
结核病可以追溯到古代，但它并不是过去的问题。每年，数百万人死于结核病。结核分枝杆菌吸入感染性飞沫核后，到达肺部，在那里它可以操纵免疫系统并在宿主巨噬细胞内存活，从而建立持续感染。信号淋巴细胞激活分子家族成员 1（SLAMF1）是一种自身配体受体，能够内化革兰氏阴性菌并调节巨噬细胞的吞噬体功能。在结核病中，SLAMF1 促进 Th1 保护性反应。在这项工作中，我们研究了 SLAMF1 在结核分枝杆菌感染期间对巨噬细胞功能的作用。我们的结果表明，结核分枝杆菌和 IFN-γ 刺激均可诱导来自健康供体和东北大学儿科 1 细胞的巨噬细胞中 SLAMF1 的表达。通过 SLAMF1 与激动性抗体的共刺激导致巨噬细胞对结核分枝杆菌的内化增强。有趣的是，我们发现 SLAMF1 与结核分枝杆菌相互作用，并与细菌以及早期和晚期内体/溶酶体标记物（EEA1 和 LAMP2）共定位，表明 SLAMF1 识别结核分枝杆菌并参与内体溶酶体成熟过程。值得注意的是，在结核病患者胸腔积液中的 CD14 细胞中检测到 SLAMF1 水平升高，表明 SLAMF1 可能在感染部位具有积极作用。总之，我们的结果提供了证据，表明 SLAMF1 可改善人单核细胞衍生的巨噬细胞对结核分枝杆菌的摄取。
