Innate lymphoid cells in HIV pathogenesis and in the human female genital tract

Women are underrepresented in HIV infection and prevention research despite making up half of people living with HIV. The female genital tract (FGT) serves as a primary site of HIV acquisition, but gaps in knowledge remain regarding protective innate immune mechanisms. Innate lymphoid cells are tissue-resident cells involved in mucosal barrier maintenance and protection, and innate lymphoid cells (ILCs) are altered during chronic HIV infection. However, ILCs role in mucosal HIV pathogenesis is unclear and they are poorly characterized in the FGT.

Human ILCs differ from their mouse counterparts and plastically adjust to their tissue of residency. Human ILC characterization is difficult due to tissue-specific adaptations and transition between subsets. While evidence for ILC involvement in antiviral activity and barrier maintenance is provided in mouse models, human ILC role in mucosal immunity remain understudied, particularly in the FGT. In chronic HIV/simian immunodeficiency virus (SIV) infection, ILCs are altered in a tissue-specific manner, and SIV models indicate potential for antiviral responses.

ILCs are tissue-resident plastic cells that provide barrier protection at mucosal surfaces and display antiviral capacity. Considering that HIV is primarily transmitted through mucosal exposure, more research is needed to understand ILC contribution to HIV pathogenesis in human mucosal surfaces relevant for HIV acquisition.