Innate immunity is the first line of defense designed to protect the host from invading pathogens, including HIV. HIV viremia is associated with a wide range of immune dysfunctions that contribute to an immunocompromised state and disease progression. Persistent HIV replication has been shown to have a broad effect on several immune cell types and/or their interactions involved in mounting an effective immune response. We have previously described several NK cell abnormalities in HIV-viremic individuals. In the past year, we investigated the integrity of plasmacytoid dendritic cell (pDC)-NK cell interactions among HIV viremic, aviremic and seronegative individuals. Our results describe: 1) a critical defect in the ability of pDCs from HIV infected individuals to secrete IFN- and TNF and subsequently activate NK cells and: 2) an inherent defect in NK cells from HIV infected individuals to respond to pDC-secreted cytokines. Furthermore, we were able to demonstrate a direct effect of HIV trimeric gp120 on NK cells in vitro similar to that described ex vivo. Finally, we were able to establish that HIV gp120-mediated suppressive effect on NK cells resulted from its binding to the integrin alpha4beta7 expressed on NK cells. These findings suggest a novel mechanism by which HIV is capable of suppressing innate immune function in infected individuals.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Intramural Research (Z01)
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