My laboratory determines whether innate lymphocyte natural killer (NK) cells kills autologous HIV-infected CD4+ T-cells cells and whether HIV controls the cytotoxic response by modulating ligands that engage receptors that trigger NK cell killing. We uncovered from these studies that several HIV-encoded proteins (i.e., Nef, Vpr and Vpu), which are key for virus replication, also control NK cells ability to kill infected cells. Our findings are critical since despite the ability of NK cells to respond to HIV-infected cells, they fail to bring it under control. Thus, HIV is able to evade a key early anti-HIV immune response in order to gain a foothold and establish itself within the host. We recently embarked on studies to determine the immunologic function of NK cells and innate lymphoid cells (ILCs) in the mucosa of the colon during HIV infection. These innate lymphocytes in the GI tract are critical during HIV infection since the virus, leads to a drastic loss of CD4+ T-cells within the mucosa of the GI tract soon after HIV Infection, dysbiosis with the gut occurs during HIV infection with decreased diversity of the microbiota and increased translocation of microbial products in the gut which inevitably leads to mucosal and systemic inflammation and immune activation. We have so far demonstrated that HIV leads to inflammatory ILCs and NK cells while retaining their ability to secrete cytokines critical for gut homeostasis. The presence of inflammatory innate lymphocytes in the gut is likely due to HIV inducing a combination of pro-inflammatory cytokines produced by myeloid dendritic cells and IL-18 secretion by IgA/IgG expressing lymphocytes in the colon. How these innate leukocytes lead to pathogenesis in infected individuals even in the presence anti-retroviral therapy will be determined in studies.
