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

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

JOURNAL OF LEUKOCYTE BIOLOGY

FEDERATION AMER SOC EXP BIOL

Año: 2021

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 HospitalPediatrcs-1 cells. Costimulation through SLAMF1 with an agonistic antibody resulted in anenhanced internalization of M. tuberculosis by macrophages. Interestingly, we found that SLAMF1interacts with M. tuberculosis and colocalizes with the bacteria and with early and late endosomes/lysosomes markers (EEA1 and LAMP2), suggesting that SLAMF1 recognize M. tuberculosisand participate in the endolysosomal maturation process. Notably, increased levels of SLAMF1were detected in CD14 cells from pleural effusions of tuberculosis patients, indicating thatSLAMF1 might have an active function at the site of infection. Taken together, our results provideevidence that SLAMF1 improves the uptake of M. tuberculosis by human monocyte-derivedmacrophages.