NEUTROPHIL AUTOPHAGY DURING HUMAN ACTIVE TUBERCULOSIS IS MODULATED BY SLAMF1

JOAQUIN M. PELLEGRINI; FLORENCIA SABBIONE; MARÍA PAULA MORELLI; CANDELA MARTIN; NANCY TATEOSIAN; CASTELLO, FLORENCIA; AMIANO, NICOLÁS; DOMINGO J. PALMERO; ALBERTO LEVI; MARÍA ISABEL COLOMBO; ANALÍA SILVINA TREVANI; VERÓNICA E. GARCIA

Tucuman

Congreso; LVII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2019

BACKGROUND: Neutrophils infected with Mycobacterium tuberculosis (Mtb) predominate in patient ́s lungs. Neutrophilic infiltration represents a characteristic feature of severe tuberculosis (TB) but neutrophil biology during TB remains poorly understood. Autophagy is crucial for several neutrophil functions and can be modulated by different mediators. The costimulator SLAMF1 acts as a microbial sensor in macrophages but its expression in human neutrophils has not been evaluated.METHODS: We investigated whether SLAMF1 participates in neutrophil autophagy against Mtb. Neutrophils were isolated from heparinized blood from TB patients and healthy donors and cultured (2x106 cells/ml) with Mtb-Ag (10μg/ml) ± SLAMF1 mAb (10μg/ml) during 2h. Some experiments were performed in the presence of a NADPH-oxidase inhibitor. SLAMF1 and autophagy levels were analyzed by flow cytometry and confocal microscopy. P values of <0.05 were considered statistically significant.RESULTS: We detected a significantly higher number of neutrophils in patients with positive Acid Fast Bacilli (AFB) in sputum as compare to negative AFB TB patients (p<0.01). Furthermore, for the first time to our knowledge, we observed SLAMF1 expression in neutrophils challenged with Mtb-Ag. Upon Mtb stimulation, neutrophils from TB patients exhibited significantly lower levels of SLAMF1 and autophagy than those from healthy donors (p<0,01). Interestingly, SLAMF1 engagement with an agonist antibody increased neutrophil autophagy induced by Mtb-Ag (p<0.001) in a ROS-dependent manner (p<0.01). Furthermore, SLAMF1 colocalized with LC3B+ vesicles.CONCLUSIONS: Altogether, our findings suggest that stimulation of SLAMF1 promotes neutrophil autophagy against Mtb, participating in the anti-mycobacterial human response during active TB.