"Neutrophils in human tuberculosis: are these cells key players in the fight against Mycobacterium tuberculosis?"

GARCÍA V.E

Congreso; Reunión Anual de Sociedades de Bociencias, 3rd French-Argentinean Immunology Congress; 2022

Tuberculosis (TB) is one of the top ten causes of death worldwide. Then, it is crucial to elucidate the host immune mechanisms that operate during Mycobacterium tuberculosis (Mtb) infection. Neutrophils are the cells predominantly infected with Mtb in patients’ lungs. Therefore, a deeper investigation into the biology of neutrophils in TB is crucial to identify specific targets for host-directed therapies. Previously, we demonstrated that autophagy collaborates with human immune responses against Mtb in close association with IFNG and that IL-17A augments autophagy in Mtb-infected monocytes from TB patients in association with the disease severity. Besides, we showed that Mtb-Ag stimulation increased SLAMF1 expression on TB patients´ neutrophils Moreover, we demonstrated that neutrophil autophagy during human TB is modulated by SLAMF1. To investigate the importance of neutrophils in the fight against Mtb, we studied the functional phenotypes of these cells in patients with different immune responses to Mtb. TB patients were classified as high responder (HR) or low responder (LR) according to their T cell responses against Mtb. Significant higher Mtb autophagy was observed in HR compared to LR. Interestingly, autophagy levels were markedly decreased by IFN-α, IL-17, IFN-γ, IL-1β in HR but not in LR. Besides, LR patients’ neutrophils secreted the highest IL-8 levels, but generated the lowest ROS. Mtb-stimulated neutrophils from HR displayed the highest levels SLAMF1 and CD69, whereas PD-L1 expression was significantly augmented in LR. Together, we demonstrated that autophagy, ROS generation and innate receptors expression in Mtb stimulated neutrophils depend on the TB patient´s immune status and could be differentially modulated by cytokines. Our findings suggest that modulation of functional phenotypes of patients with different immune status to Mtb might contribute to the development of new immunotherapies to control active TB.