HIV-1/Mycobacterium tuberculosisCoinfection Immunology: How Does HIV-1 Exacerbate Tuberculosis?

Abstract

Human immunodeficiency virus type 1 (HIV) and Mycobacterium tuberculosis have become intertwined over the past few decades in a "syndemic" that exacerbates the morbidity and mortality associated with each pathogen alone. The severity of the coinfection has been extensively examined in clinical studies. The extrapolation of peripheral evidence from clinical studies has increased our basic understanding of how HIV increases susceptibility to TB. These studies have resulted in multiple hypotheses of how HIV exacerbates TB pathology through the manipulation of granulomas. Granulomas can be located in many tissues, most prominently the lungs and associated lymph nodes, and are made up of multiple immune cells that can actively contain M. tuberculosis. Granuloma-based research involving both animal models and clinical studies is needed to confirm these hypotheses, which will further our understanding of this coinfection and may lead to better treatment options. This review examines the data that support each hypothesis of how HIV manipulates TB pathology while emphasizing a need for more tissue-based experiments.

Aberrant Inflammasome Activation Characterizes Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome

“…+ T cell deficiency results in decreased IFN-g activation of macrophages and intracellular killing of M. tuberculosis (52,53), leading to an accumulation of M. tuberculosis intracellularly and eventually activation of inflammasomes (54). In the present study, we provide evidence that failure to control M. tuberculosis replication in monocytes/macrophages because T cell responses are impaired by HIV-induced CD4 + T cell depletion leads to "default" immune control mechanisms that include inflammasome activation in monocytes, and that this is greatest in those HIV/TB patients who subsequently develop TB-IRIS after cART is commenced.…”

Characterization of the OSSN Microbiome in HIV-1 Infected Patients

“…HIV-1 causes the depletion of CD4 T cells contributing to susceptibility of coinfected individuals to TB, as this T cell subset is significant in the control of TB and a majority of HIV-1 infected individuals are now coinfected with TB (Diedrich & Flynn, 2011).…”

Side Effects of the Immune System: Lessons from Tuberculosis-Related Immune Reconstitution Inflammatory Syndrome

“…HIV causes a strong reduction in peripheral, mucosal, and gut CD4 T cells shortly after infection by preferentially infecting activated CD4 T cells and resting memory CD4 T cells (7). However, immunologic changes during HIV/TB coinfection seem to be more complex.…”

“…A number of hypothesis have been proposed to explain how HIV could impair the ability to control Mtb infection (7).…”