SLAMF1 signaling induces Mycobacterium tuberculosis uptake leading to endolysosomal maturation in human macrophages,Journal of Leukocyte Biology

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SLAMF1 signaling induces Mycobacterium tuberculosis uptake leading to endolysosomal maturation in human macrophages
Journal of Leukocyte Biology ( IF 3.6 ) Pub Date : 2020-09-29 , DOI: 10.1002/jlb.4ma0820-655rr
Angela María Barbero _{1,

2} , Aldana Trotta ₃ , Melanie Genoula ₃ , Rodrigo Emanuel Hernández Del Pino _{1,

2} , Martín Andrés Estermann _{1,

4} , Josefina Celano ₁ , Federico Fuentes ₃ , Verónica Edith García _{5,

6} , Luciana Balboa ₃ , Paula Barrionuevo ₃ , Virginia Pasquinelli _{1,

2}

Affiliation

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.

中文翻译：

SLAMF1信号传导诱导结核分枝杆菌的摄取，导致人类巨噬细胞的溶酶体成熟

结核病可以追溯到远古时代，但这不是过去的问题。每年，有数百万人死于结核病。吸入感染性小滴核后，结核分枝杆菌到达肺，在那里它可以操纵免疫系统并在宿主巨噬细胞内存活，从而建立持续的感染。信号转导的淋巴细胞激活分子家族成员1（SLAMF1）是一种自配体受体，可以使革兰氏阴性细菌内化并调节巨噬细胞的吞噬功能。在结核病中，SLAMF1促进Th1保护反应。在这项工作中，我们研究了SLAMF1在结核分枝杆菌感染过程中对巨噬细胞功能的作用。我们的结果表明，结核分枝杆菌IFN-γ和IFN-γ刺激诱导健康供体和东北医院Pediatrcs-1细胞巨噬细胞中SLAMF1的表达。通过SLAMF1与激动性抗体的共刺激导致巨噬细胞增强了结核分枝杆菌的内在化。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的内体/溶酶体标记（EEA1和LAMP2）共定位，这表明SLAMF1可以识别结核分枝杆菌。并参与溶酶体的成熟过程。值得注意的是，在结核病患者胸腔积液的CD14细胞中检测到SLAMF1水平升高，表明SLAMF1在感染部位可能具有活性。综上所述，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吸收。

更新日期：2020-09-29

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