Nitric oxide: friendly rivalry in tuberculosis

Abstract

Immune dependent growth and development of infectious agents and pathogenesis are increasingly being recognized as crucial for designing efficient immunotherapeutic approaches for Mycobacterium tuberculosis. Nitric oxide (NO) in the context of mycobacterial infection is an essential component of the protective armory of host innate immune system. However, the ability of NO to suppress host immune response questions the traditional view that production of NO is actually designed for anti-microbial mechanism. Human tuberculosis is considered as a prime example of a disease controlled dominantly by cell-mediated and not by humoral immunity. Interleukins like IL-12 and IL-8 play important roles in anti-tuberculosis immunity. While IL-8 has a central role in leukocyte recruitment to areas of granuloma formation, IL-12 helps in the generation of effective cell-mediated immune response in tuberculosis. NO shows an ability to inhibit mycobacterial infection by inducing innate-cytotoxic response and by increasing IL-8 induction. However, it may become a problem in later phase when it converts a protective Th1 response to a subversive Th2 response mainly by inhibiting IL-12 cytokine, thus acting as a potential regulator of Th1/Th2 response. This review intends to explore the possibilities that can be envisioned for exploring NO from immunotherapeutic perspectives in mycobacterial immunity.