SLAMF1 signaling induces Mycobacterium tuberculosis uptake leading to endolysosomal maturation in human macrophages

Abstract

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 IFNstimulation 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.

Unveiling the threat: Characterization of Clostridioides difficile Infection in the Northwest Region of Buenos Aires between 2019-2023 and Associated Risk Factors redefined through a Meta-Analysis

“…Previous work evaluating platelet count in CDI episodes reported controversial results, assigning them both a beneficial and detrimental role in relation to clinical symptoms [76][77][78][79][80][81][82][83][84][85] . We have recently shown that platelets bind to C. difficile and promote its uptake by human macrophages using macropinocytic pathways 86 . Therefore, we consider that platelets in CDI could be fundamental for the resolution of the infection and that further studies are needed to unravel their role during CDI.…”

Platelets promote human macrophages-mediated macropinocytosis of Clostridioides difficile

“…0.5 x 10 6 /ml CD14 positive-selected monocytes were cultured at 37°C and 5% CO2 for 2h in absence of FBS to promote adherence. Non-adherent cells were removed and adherent cells were cultured for additional 16-18h in complete media as described before (Barbero et al, 2021) (Supplementary Figure 1A).…”

“…2 × 10 5 macrophages/well were cultured in chamber-slides (Nunc) as described before (Barbero et al, 2021). Cells were stimulated with CDH FITC and/or WP at the ratios indicated above in the presence or absence of endocytosis inhibitors.…”