NEUTROPHIL AUTOPHAGY IS MODULATED BY SLAMF1 DURING HUMAN ACTIVE TUBERCULOSIS

MORELLI MARIA PAULA; PALMERO DOMINGO; MARÍA ISABEL COLOMBO; SABBIONE FLORENCIA; AMIANO NICOLAS; CIALLELLALORENA M.; GARCIA VERONICA; PELLEGRINI JOAQUÍN; TATEOSIAN NANCY; LEVIALBERTO; TREVANI ANALÍA SILVINA

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2020; 2020

Neutrophils infected with Mycobacterium tuberculosis (Mtb) predominate in tuberculosis (TB) patients? lungs and phagocytose the pathogen but the mechanism of microbial elimination is controversial. Autophagy, a crucial mechanism for several neutrophil functions, can be modulated by immunological mediators. Besides, the costimulatory molecule SLAMF1 can function as a microbial sensor and also interact with autophagy-related proteins in macrophages. Therefore, we investigated whether SLAMF1 participates in neutrophil autophagy against Mtb. Neutrophils isolated from heparinized blood from TB patients and healthy donors (2x106 cells/ml) were infected with MtbH37Rv strain (MOI:1) during 2h or stimulated with Mtb-Antigen (Mtb-Ag,10µg/ml) or different mycobacterial compounds. In several experiments, SLAMF1 mAb (10µg/ml) was added to cell cultures to activate this receptor. Additionally, experiments including NADPH-oxidase, ERK or p38 inhibitors were performed as well. SLAMF1 and autophagy levels were analyzed by flow cytometry and confocal microscopy. Interestingly, in concordance with bioinformatics analyses, we demonstrated for the first time that Mtb induces surface expression of SLAMF1 in human neutrophils. Moreover, we observed that diverse mycobacterial components might be recognized by these cells during Mtb infection and induce SLAMF1 surface expression through ROS and MAPK activation (p