Human Immune mechanisms that operate during TB infection

GARCÍA, VERÓNICA E

Congreso; Reunión conjunta SAIC-SAFE-SAB-SAP 2019; 2019

Mycobacterium tuberculosis (Mtb) is the major cause of death by a microbiological agent,causing nearly 1.6 million of deaths per year. In Argentina, last reports estimated 10.733 casesof tuberculosis and almost 1000 deaths annually. Therefore, it is crucial to elucidate the hostimmune mechanisms that operate during Mtb infection. The collaboration between antigenpresenting cells and lymphocytes culminating in their mutual activation is mediated by therelease of cytokines and other effector molecules. Accordingly, reduced IFNG production is amarker of severe disease. In line with this, we demonstrated that the activation of signalingproteins like SLAM and ICOS increased Th1 lymphocytes against Mtb, whereas PD-1, CD31and SAP induction inhibited this population. Moreover, we found a direct association betweenTh1+Th17+ lymphocytes expanded by Mtb and active tuberculosis severity. Additionally, amongdefense mechanisms against Mtb, autophagy is an essential process that modulates thesecretion of key cytokines against the pathogen and constitutes a direct mechanism of bacterialelimination. Besides, autophagy can be modulated by cytokines and other immunologicalsignals. Thus, efforts are needed to further elucidate the basic mechanisms of autophagy inimmunity against mycobacteria. Then, we used primary cells from blood from tuberculosispatients to understand the pathways that regulate autophagy during active disease. Wedemonstrated that: i) autophagy collaborates with human immune responses against Mtb inclose association with specific IFNG secreted against the pathogen; ii) IL-17A augmentsautophagy in Mtb-infected monocytes from tuberculosis patients in association with the severityof the disease; iii) different mediators regulate autophagy in neutrophil from tuberculosispatients. Together, our findings suggest that modulation of specific host immune pathwaysmight contribute to the development of new immunotherapies to control active tuberculosis