BLOCKING PD-1 RESCUES PROTECTIVE T CELL RESPONSE TO FACILITATE BACILLARY CLEARANCE AND MODULATION OF THE EFFLUX PUMP EXPRESSION OF MYCOBACTERIUM TB

Abstract

TYPE: Late Breaking Abstract TOPIC: Chest Infections PURPOSE: Previously, we have shown the critical role of regulatory Treg cells and PD-1 pathway in causing suppressed state of Tcell response against Mycobacterium tuberculosis among TB patient. In this study, we attempted to understand the status of host immune response among the MDR and Drug Sensitive TB patients. We also checked the contribution of PD-1 pathway on poly-functional Tcells,critical for protective immunity in TB. METHODS: For immune response profile and invitro experiments, polychromatic flowcytometry based immunological assays were performed.PD1 blocking experiments were performed in mice infected with Mtb. RESULTS: We observed rescue of PFTS in TB patients by blocking PD-1.We also observed that PFTs (IFN-γ+ TNF-α+) undergo apoptosis in TB patients due to higher expression of PD-1.Blocking PD-1 pathway in vivo among mice infected with Mtb, demonstrated restoration of PFTs with enhanced reduction of bacillary load. We observed increase in the frequency of Tregs whereas decrease in the PFTs response in Drug Resistant as compared to Drug Sensitive TB patients. Furthermore, we observed modulation of efflux pump of M.tb by pro-inflammatory (IFN-γ , TNF-α) and anti-inflammatory cytokines (IL-10 and TGF-β) in invitro MDM model. CONCLUSIONS: Our results demonstrate elicitation of weaker effector T cell response in DR TB compared to DS TB patients.Our results showed that rescuing appropriate immune response improves the efficacy of anti-tubercular therapy in TB. CLINICAL IMPLICATIONS: Our findings suggest critical role of PD-1 in suppressing the protective immune response in TB. Rescuing PFTs by blocking PD-1 pathway may offer a novel strategy for adjunct immunotherapy in TB. DISCLOSURE: Nothing to declare. KEYWORD: Tuberculosis PD1 Regulatory T cells Polyfunctional T cells