Challenges faced by the immune response towards HIV and mycobacterium tuberculosis co-infection

Abstract

Mycobacterium luberc11/osis is responsible for an extremely important life-lhreatening disease, which affects approximately one third of the world's population. Tuberculosis (TB) claims more lives than any olher single infectious disease. Despite the availability of the Bacille Calmette-Guérin (BCG) vaccine and lhe widespread implementation of Directly Observed Short-Course (DOTS), TB has emerged as a major complication of HIV infection in both developing and industrialized countries. Using different pathways, M. 111berc11/osis infects macrophages, its preferential habitat, which paradoxically are the chief effector cells for killing mycobacteria. The balance between these functions determines lhe outcome of infection. As an intracellular palhogen, protective immunity to M. tubercu/osls requires Cell­Mediated lmmunity (CMn, which major effcctor mechanism is the activation of infected macrophages by type-1 cytokincs, particularly interferon-y, produced primarily by Th-1 CD4. lymphocytes, in response to macrophage products, such as interleukin-12. Cytotoxic T Lymphocyte (CTL) response mediated by CD8 + cells also participate in cffective CMI against mycobacteria. Human Immunodeficiency Virus (HJV) infection is detrimental to M. tuberculosis-infected patients increasing lhe risk for both primary and reactivation TB, and for second episodes ofTB from exogenous re-infection. The immunologica\ explanation has become evident: both pathogens require Th-1 type response, which is compromised in both infections. TB has also had a great impact on HJY: HIV replicates more efficiently in activated T cells and virai leveis increase consistently when lhe immune system is activated by exogenous stimuli, such as M. iuberc11/osis. Toe increase in virai replication is assÓciated with cytokines released by the activated macrophage, particularly tumor necrosis factor-a and interleukin-1. M. 1UberC11losis also induces nuc.lear factor kappa-B, a cellular factor that binds to promoter regions of HIV, enhancing its replication. Early identific\ltion of HJV-TB coinfection is crucial for prompt anti-mycobacterial and anti-retroviral therapeutic interventions, before deterioration of lhe immune system occurs, resulting in improved survival of lhe patients.