Grant: Operating Grant

Many sexually transmitted viral pathogens (STV) occur mainly through entry via mucosal surfaces into their human hosts. Today, more than 35 million people are living with HIV worldwide and this disease remains one of the major global health problems. The main entry portals of HIV-1 during sexual transmission are the mucosal surfaces of the female and male genital and/or rectal tracts. Understanding how the immune system respond to viral infection in mucosal tissues represents a central question for HIV-infected individuals. However, vaginal and rectal mucosal tissues are quite distinct in anatomy, physiology, and immunobiology, and these characteristics can dramatically influence the efficiency of controlling HIV dissemination. Recently, successful control of several STV infections has been associated with the presence of sustained local immune response related to a novel leukocyte population called tissue-resident memory (Trm) CD8 T cells. However, dynamics and functions of this novel cell population in mucosal tissues have never been addressed in the context of HIV infection. In this study, we propose to characterize this population in mucosal tissues compared to non-mucosal tissues including peripheral blood, lymph nodes and spleen. As it is essential to determine their changes early after viral exposure, we will conduct this project using non-human primate models comparing pathogenic rhesus macaques, which develop AIDS and non-pathogenic African green monkeys, which are resistant to AIDS. These models offer a unique opportunity to analyze deep tissues, which are not easily accessible in humans, particularly early after infection. The findings obtained during this project are of considerable interest in order to better understand mucosal immunity in HIV-infected individuals since this novel population represents a potent new immune effector cells involved on STV control in mucosal tissues, the first sites of HIV viral exposure.