Pattern recognition receptors and coordinated cellular pathways involved in tuberculosis immunopathogenesis: Emerging concepts and perspectives

Abstract

Pattern Recognition Receptors (PRRs) play a central role in the recognition of numerous pathogens, including Mycobacterium tuberculosis, resulting in activation of innate and adaptive immune responses. Besides Toll Like Receptors, C-type Lectin Receptors and Nod Like Receptors are now being recognized for their involvement in inducing immune response against M. tuberculosis infection. Although, a functional redundancy of the PRRs has also been reported in many studies, emerging evidences support the notion that a cooperative and coordinated response generated by these receptors is critical to sustain the full immune control of M. tuberculosis infection. Many of the PRRs are now found to be involved in various cellular host defenses, such as inflammasome activation, phagosome biogenesis, endosomal trafficking, and antigen processing pathways that are all very critical for an effective immune response against M. tuberculosis. In support, polymorphism in several of these receptors has also been found associated with increased susceptibility to tuberculosis in humans. Nonetheless, increasing evidences also show that in order to enhance its intracellular survival, M. tuberculosis has also evolved multiple strategies to subvert and reprogram PPR-mediated immune responses. In light of these findings, this review analyzes the interaction of bacterial and host factors at the intersections of PRR signaling pathways that could provide integrative insights for the development of better vaccines and therapeutics for tuberculosis.