Natural cytotoxicity receptor NKp44 and NK - astrocyte interactions in HIV-associated neurocognitive disorders (INM1P.443)

Abstract

Abstract NK cells play important role in immunity against pathogens and cancer. NK cell functions are regulated by inhibitory and activating receptors binding corresponding ligands on the surface of target cells. NK cells were shown to be recruited to the CNS following several pathological conditions. NK cells could impact CNS physiology by killing glial cells and by secreting IFN-g. Astrocytes are intimately involved in immunological and inflammatory events occurring in the CNS and reactive astrogliosis is a key feature in HIV-associated neurocognitive disorders (HAND). There is little data on NK-astrocyte interactions and ligands expressed on astrocytes that could impact NK cell function. Natural cytotoxicity receptors (NCRs) play critical role in the cytolytic function of NK cells. Here we have studied the expression and function of natural cytotoxicity receptor NKp44 upon NK-astrocyte interactions in the presence or absence of an HIV peptide (3S peptide) shown to induce NK cell killing of CD4+ T cells during HIV infection. Using a fusion protein consisting of the extracellular domain of NKp44 and human IgG Fc, we determined the expression of a novel ligand for NKp44 (NKp44L) on astrocytes. Incubation of astrocytes with 3S peptide downregulated NKp44L expression on astrocytes implicating protection from NK mediated killing. Thus, our study showed that NKp44 has a protective effect on astrocytes from NK cell mediated killing during HIV infection and impacts astrocyte role in HAND.