SLAM MEDIATES MYCOBACTERIUM TUBERCULOSIS RECOGNITION AND ENDOLYSOSOMAL MATURATION IN HUMAN MONOCYTE-DERIVED MACROPHAGES .

BARBERO AM; HERNÁNDEZ DEL PINO RE; TROTTA A; GENOULA M; ESTERMANN MA; CELANO J; FUENTES F; GARCÍA VE; BALBOA L; BARRIONUEBO P; PASQUINELLI V

Congreso; 8th Annual Meeting of the International Cytokine and Interferon Society; 2020

Tuberculosis is the leading cause of death from a single infectious agent in the world. Mycobacteriumtuberculosis has smartly manipulated the immune system to survive within host macrophages over ages. The SignalingLymphocytic Activation Molecule (SLAM) is a self-ligand receptor that internalizes Gram- bacteria and regulates macrophages? phagosomal functions. In Tuberculosis, SLAM promotes Th1 protective immune responses. In this work, we studied SLAM role on macrophages? functions against M. tuberculosis infection.Human monocyte-derived macrophages were obtained from healthy donors by CD14 positive selection. After 2h of adherence, cells were cultured in complete media overnight before stimulation with sonicated-M. tuberculosis (Mtb). THP1 cells were differentiated with PMA for 24h before Mtb stimulation.We observed that both Mtb and rhIFN-g stimulation induce SLAM expression in monocyte-derived macrophages and THP-1 cells, as determined by flow cytometry (FC). No changes where observed with rhIL-4 and rhIL-10 treatment.Moreover, rhIFN-g increased TNF-α secretion in Mtb-stimulated THP-1 cells. However, SLAM did not regulate TNF-α nor IL-1β production as measured by ELISA.Rhodamine-stained Mtb (Mtb-R) or live M. tuberculosis-RFP were used to evaluate SLAM role on bacterial uptake by FC. Costimulation trough SLAM with an agonistic antibody further induced Mtb-R and M. tuberculosis-RFP endocytosis by macrophages and THP-1 cells (p