HIV compromises Th17 and Th22 immunity in a humanized mouse model of Tuberculosis and HIV co-infection

Tuberculosis (TB) kills an estimated 1–2 million people per year and is the leading cause of death in people with HIV (PWH). The CD4+ T helper (Th) populations play significant roles in protective immunity to Mycobacterium tuberculosis (Mtb), and are also important host cells for HIV proliferation and persistence. Emerging evidence in PWH suggests that Th17 and Th22 cells may be preferentially depleted during HIV infection, an outcome that could pose a risk for Mtb containment during co-infection. We employed our humanized mouse model of co-infection to assess pulmonary and peripheral changes in Th17 and Th22 frequency and function due to infection with HIV, Mtb, or both. As determined with multi-plex ELISA, co-infection with HIV suppressed the cytokine response to Mtb including IL-17A, IL-22, IL-6, and IL-1β. Multi-parameter flow cytometric analysis revealed that Mtb and HIV/Mtb infection led to increased Th17+ cells in lung and decreased Th17+ cells in spleen. Following HIV or HIV/Mtb infection, Th22+ cells were significantly decreased in both lung and spleen. Importantly, HIV preferentially infected Th17 cells compared to Th22 and other Th subpopulations. Greater HIV viral load was also observed in the lung, but not spleen, of animals with Mtb/HIV co-infection compared to those with HIV mono-infection. Overall, these results suggest that HIV may compromise Th22 immunity, and exploit Th17+ cells to promote viral pathogenesis, in the setting of Mtb and HIV co-infection. Y.B. Martinez-Martinez is supported by Conacyt-I2T2 in Mexico, Contex, and the James W. McLaughlin Fellowship Fund. Grant support was provided by NIH R01AI147948 award to J. Endsley