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

TROTTA, ALDANA; ESTERMANN, MARTÍN ANDRÉS; GARCÍA, VERÓNICA EDITH; PASQUINELLI, VIRGINIA; GENOULA, MELANIE; CELANO, JOSEFINA; BALBOA, LUCIANA; BARBERO, ANGELA MARÍA; PINO, RODRIGO EMANUEL HERNÁNDEZ DEL; FUENTES, FEDERICO; BARRIONUEVO, PAULA

JOURNAL OF LEUKOCYTE BIOLOGY

FEDERATION AMER SOC EXP BIOL

Año: 2020

0741-5400

Tuberculosis dates back to ancient times but it is not a problem of the past. Each year, millionsof people die from tuberculosis. After inhalation of infectious droplet nuclei, Mycobacteriumtuberculosis reaches the lungs where it can manipulate the immune system and survive withinhost macrophages, establishing a persistent infection. The signaling lymphocytic activationmolecule family member 1 (SLAMF1) is a self-ligand receptor that can internalize gram-negativebacteria and regulate macrophages? phagosomal functions. In tuberculosis, SLAMF1 promotesTh1-protective responses. In this work, we studied the role of SLAMF1 on macrophages? functionsduring M. tuberculosis infection. Our results showed that both M. tuberculosis and IFN-𝛾stimulation 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-derivedmacrophages.