HIV impairs and exploits pulmonary Th17 and Th22 cell-mediated immune responses to Mycobacterium tuberculosis

Tuberculosis (TB), caused by the bacteria Mycobacterium tuberculosis (Mtb), is the world's leading cause of death by infectious disease, as well as the leading cause of death in people with HIV. The cytokines interleukin (IL)-17 and IL-22 are chemical messengers that are essential for a protective immune response to Mtb infections and tissue repair following bacterial clearance, respectively. The CD4+ T cell subsets that are primary sources of these cytokines, Th17 and Th22 cells, are also primary targets for HIV infection at mucosal surfaces like the gut and lung. Our work reveals Th17 as important HIV viral reservoirs in organs of Mtb/HIV co-infection, with defective immune signals compared to Mtb single infection in the humanized mouse model. Th22 responses were also decreased by HIV in both mono- and Mtb/HIV co-infection as early as nine days after infection. These results have potential applications for future TB therapeutic vaccine design and may implicate possible targets to augment TB therapy. Overall design: RNA-seq profiling lung tissues of mouse with human immune stem cells either mock infected, infected with TB, infected with HIV, or co-infected with TB and HIV.