OA04.02
Background: Innate Lymphoid Cells (ILCs) lack rearranged antigen receptors but share functional and developmental characteristics with lymphocytes and can be subdivided into three main groups according to their production of Th1, -Th2 and -Th17 cell-associated cytokines named ILC1, ILC2 and ILC3s, respectively. ILCs play a crucial role in tissue homeostasis and repair in both non-infectious and infectious diseases. HIV-1 pathology involves lymphoid tissue destruction of the gut mucosa associated with microbial translocation, immune activation and disease progression in both ARV-treated and untreated individuals. We hypothesized that HIV modulates the ILC population in blood and tissue.
Methods: We used phenotypic and transcriptional characterization of human ILCs from a total of n=83 chronic HIV-infected and n=64 HIV uninfected individuals recruited from 4 different cohorts in Durban, South Africa.
Results: We show that the Th2 cytokine producing ILC2 population in human peripheral blood is severely depleted in viremic HIV-1 infected individuals (P<0.0001) but preserved in those with natural immune control of HIV-1 (P=0.003), and correlates negatively with plasma viral load (r=-0.62, P=0.0004). This ILC2 population is depleted from peripheral blood within 20 days of HIV-1 transmission (P=0.04) and only partially restored upon successful antiretroviral therapy in a subset of individuals. Similar depletion of ILC1 and ILC3 populations were observed in chronic infection (P<0.001) to similar kinetics as the ILC2 population, but distinct from the observed NK cell expansion dynamics. Preliminary data from gut and tonsil tissue resident cells shows overall reduction of ILCs skewed towards an NCR3+ ILC3 population.
Conclusions: These data demonstrate that HIV-1 infection rapidly and profoundly modulates the tissue resident and circulating ILC population, with great potential significance to the pathology of this disease.
