Abstract
Tuberculosis (TB) is a common opportunistic infection and the leading cause of death for human immunodeficiency virus (HIV)-infected patients. Thus, it is necessary to understand the pathogenetic interactions between M.tb and HIV infection. In this study, we examined M.tb and/or simian immunodeficiency virus (SIV) infection of Chinese rhesus macaques. While there was little evidence that M.tb enhanced SIV infection of macaques, SIV could facilitate M.tb infection as demonstrated by X-rays, pathological and microbiological findings. Chest X-rays showed that co-infected animals had disseminated lesions in both left and right lungs, while M.tb mono-infected animals displayed the lesions only in right lungs. Necropsy of co-infected animals revealed a disseminated M.tb infection not only in the lungs but also in the extrapulmonary organs including spleen, pancreas, liver, kidney, and heart. The bacterial counts in the lungs, the bronchial lymph nodes, and the extrapulmonary organs of co-infected animals were significantly higher than those of M.tb mono-infected animals. The mechanistic studies demonstrated that two of three co-infected animals had lower levels of M.tb specific IFN-γ and IL-22 in PBMCs than M.tb mono-infected animals. These findings suggest that Chinese rhesus macaque is a suitable and alternative non-human primate model for SIV/M.tb coinfection studies. The impairment of the specific anti-TB immunity is likely to be a contributor of SIV-mediated enhancement M.tb infection.
Highlights
Mycobacterium tuberculosis (M.tb) and human immunodeficiency virus (HIV) remain severe dualepidemics globally
TB is one of the most common opportunistic infections for people infected with HIV, even when CD4 cells count and antiretroviral therapy are taken into account (Suchindran et al, 2009)
Because people with HIV/acquired immune deficiency syndrome (AIDS) carry a high risk of M.tb infection and disease severity, it is clinically significant to have an experimental animal model that mimics M.tb and HIV coinfection
Summary
Mycobacterium tuberculosis (M.tb) and human immunodeficiency virus (HIV) remain severe dualepidemics globally. In 2014, an estimated 9.6 million people worldwide suffered from active tuberculosis (TB) and more than 34 million people were living with HIV (WHO, 2015). M.tb and HIV have been closely linked since the emergence of acquired immune deficiency syndrome (AIDS). Among the 9.6 million new TB infections worldwide, 1.2 million (13%) were HIV seropositive. HIV-infected individuals who are infected with M.tb are much more likely to develop severe TB disease than those who are HIV negative.
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