Abstract
There were an estimated 10 million new cases of tuberculosis (TB) disease in 2019. While over 90% of individuals successfully control Mycobacterium tuberculosis (Mtb) infection, which causes TB disease, HIV co-infection often leads to active TB disease. Despite the co-endemic nature of HIV and TB, knowledge of the immune mechanisms contributing to the loss of control of Mtb replication during HIV infection is lacking. Mucosal-associated invariant T (MAIT) cells are innate-like T cells that target and destroy bacterially-infected cells and may contribute to the control of Mtb infection. Studies examining MAIT cells in human Mtb infection are commonly performed using peripheral blood samples. However, because Mtb infection occurs primarily in lung tissue and lung-associated lymph nodes, these studies may not be fully translatable to the tissues. Additionally, studies longitudinally examining MAIT cell dynamics during HIV/Mtb co-infection are rare, and lung and lymph node tissue samples from HIV+ patients are typically unavailable. Nonhuman primates (NHP) provide a model system to characterize MAIT cell activity during Mtb infection, both in Simian Immunodeficiency Virus (SIV)-infected and SIV-naïve animals. Using NHPs allows for a more comprehensive understanding of tissue-based MAIT cell dynamics during infection with both pathogens. NHP SIV and Mtb infection is similar to human HIV and Mtb infection, and MAIT cells are phenotypically similar in humans and NHPs. Here, we discuss current knowledge surrounding MAIT cells in SIV and Mtb infection, how SIV infection impairs MAIT cell function during Mtb co-infection, and knowledge gaps to address.
Highlights
Mucosal-associated invariant T (MAIT) cells are intriguing in the context of HIV and Mycobacterium tuberculosis (Mtb) infection because they reside in mucosal sites, such as the rectal mucosa and lungs [7,8,9], where the host initially encounters HIV and Mtb, respectively
We discuss how Nonhuman primates (NHP) models of Simian Immunodeficiency Virus (SIV), Mtb, and SIV/Mtb have been used to improve our understanding of MAIT cell dynamics longitudinally and within inaccessible tissues affected by SIV and Mtb
MAIT cells isolated from the peripheral blood of active TB patients and stimulated in vitro with Escherichia coli had significantly decreased IFNγ production when compared to healthy controls [49]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. MAIT cells are intriguing in the context of HIV and Mycobacterium tuberculosis (Mtb) infection because they reside in mucosal sites, such as the rectal mucosa and lungs [7,8,9], where the host initially encounters HIV and Mtb, respectively. These tissue sites are often difficult to access in human studies, necessitating the use of animal models. We discuss how NHP models of SIV, Mtb, and SIV/Mtb have been used to improve our understanding of MAIT cell dynamics longitudinally and within inaccessible tissues affected by SIV (i.e., lymph nodes) and Mtb (i.e., lungs and granulomas)
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