Latent tuberculosis

Biology

Mycobacterium tuberculosis

Viral replication

Virology

T cell

Chronic infection

Immunology

Simian immunodeficiency virus

Immune system

Human immunodeficiency virus (HIV)

Tuberculosis

Medicine

Virus

Pathology

Trends in Microbiology

A third of all 1.5 million annual deaths due to tuberculosis (TB) have an HIV component. The mere depletion of lung CD4+ T cells is insufficient in causing reactivation in macaques with latent TB infection (LTBI). These findings suggest a critical role for CD4+ T cell-independent factors such as chronic immune activation and altered effector T cell phenotypes in the reactivation of LTBI in Mtb/SIV co-infection. The approaches discussed herein represent the ideal use of knowledge gained from decades of work on two of the deadliest microbes known to humanity – Mtb and HIV – to develop translational approaches towards the control of the TB/AIDS syndemic. HIV co-infection is the most critical risk factor for the reactivation of latent tuberculosis (TB) infection (LTBI). While CD4+ T cell depletion has been considered the major cause of HIV-induced reactivation of LTBI, recent work in macaques co-infected with Mycobacterium tuberculosis (Mtb)/simian immunodeficiency virus (SIV) suggests that cytopathic effects of SIV resulting in chronic immune activation and dysregulation of T cell homeostasis correlate with reactivation of LTBI. This review builds on compelling data that the reactivation of LTBI during HIV co-infection is likely to be driven by the events of HIV replication and therefore highlights the need to have optimum translational interventions directed at reactivation due to co-infection. HIV co-infection is the most critical risk factor for the reactivation of latent tuberculosis (TB) infection (LTBI). While CD4+ T cell depletion has been considered the major cause of HIV-induced reactivation of LTBI, recent work in macaques co-infected with Mycobacterium tuberculosis (Mtb)/simian immunodeficiency virus (SIV) suggests that cytopathic effects of SIV resulting in chronic immune activation and dysregulation of T cell homeostasis correlate with reactivation of LTBI. This review builds on compelling data that the reactivation of LTBI during HIV co-infection is likely to be driven by the events of HIV replication and therefore highlights the need to have optimum translational interventions directed at reactivation due to co-infection. Chronic Immune Activation in TB/HIV Co-infection: (Trends in Microbiology , 619–632; 2020)Sharan et al.Trends in MicrobiologyMay 29, 2020In BriefWith respect to the first version that was online, the fourth paragraph of the section "Mitigation of Chronic Immune Activation", which begins with "Another promising strategy to suppress immune activation," changed: reference numbers were corrected, text changed and two sentences were removed. Because of the renumbering of references, the reference numbers of several other references were adapted. Full-Text PDF

Chronic Immune Activation in TB/HIV Co-infection