Evaluation of epigenetic and immune alterations of macrophages from patients infected with human immunodeficiency virus in response to Mycobacterium tuberculosis

Abstract

In developing countries including Brazil, the HIV-1 infection is a major cause of death attributed to infectious diseases, especially when associated with opportunistic coinfections, such as tuberculosis, which affects one third of patients infected with HIV. Macrophages have an essential role in both diseases, they are the reservoir and site of intracellular growth of both pathogens, in addition, they are key cells to the elimination of Mycobacterium tuberculosis. However, several studies show that HIV infection reduces the viability of macrophages, deregulates the proinflammatory signals and the main effector mechanisms of the cell, thereby increasing the replication ability of both pathogens. However, little is known about the molecular events induced by HIV that causes reduced immune responsiveness of macrophages. Moreover, it is known that epigenetic alterations can regulate the transcription and expression of some key genes for the control or susceptibility to disease. Therefore, in this work, we aim to study whether HIV infection induces epigenetic changes and if those changes result in regulation of the immune response genes on macrophages, when these cells are infected in vitro by M. tuberculosis.