Role Of Innate Immunity In The Initiation And Pathogenes

Fauci, Anthony S.

Abstract

Innate immunity is the first line of defense designed to protect the host from invading pathogens, including HIV. We have previously demonstrated that natural killer (NK) cell- mediated suppression can be potent and that it is related to the stage of HIV infection as well as the level of HIV plasma viremia. Our study revealed that HIV viremia impairs the ability of NK cells to secrete CC-chemokines and alters the expression of various inhibitory and chemokine receptors expressed on NK cells. Further analysis of NK-cell specific surface receptors revealed upregulation of inhibitory NK receptors and chemokine receptor CCR5. In addition, our data showed CCR5 upregulation to be induced as a result of immune activation while induction of iNKRs appeared to be a direct result of an HIV-induced effect. Analysis of NK cell interactions with R5 and X4 HIV envelopes showed profound suppression of generic NK cell function upon exposure to these envelopes. DNA microarray analyses of NK cells from HIV viremic patients showed upregulation of genes induced by interferon. Further studies will address the HIV-NK cell interactions and explore the cellular and molecular basis for this suppressive effect.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000886-03
• Application #: 6809118
• Study Section: (LIR)
• Support Year: 3
• Fiscal Year: 2003

Institution

• Name: Niaid Extramural Activities
• Country: United States

Publications

Kottilil, Shyam; Yan, Michael Y; Reitano, Kristin N et al. (2009) Human immunodeficiency virus and hepatitis C infections induce distinct immunologic imprints in peripheral mononuclear cells. Hepatology 50:34-45

Chun, Tae-Wook; Nickle, David C; Justement, Jesse S et al. (2008) Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy. J Infect Dis 197:714-20

Cortez, Karoll J; Roilides, Emmanuel; Quiroz-Telles, Flavio et al. (2008) Infections caused by Scedosporium spp. Clin Microbiol Rev 21:157-97

Moir, Susan; Malaspina, Angela; Ho, Jason et al. (2008) Normalization of B cell counts and subpopulations after antiretroviral therapy in chronic HIV disease. J Infect Dis 197:572-9

Tilton, John C; Manion, Maura M; Luskin, Marlise R et al. (2008) Human immunodeficiency virus viremia induces plasmacytoid dendritic cell activation in vivo and diminished alpha interferon production in vitro. J Virol 82:3997-4006

Arthos, James; Cicala, Claudia; Martinelli, Elena et al. (2008) HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells. Nat Immunol 9:301-9

Neumann, Au; Polis, Ma; Rozenberg, L et al. (2007) Differential antiviral effect of PEG-interferon-alpha-2b on HIV and HCV in the treatment of HIV/HCV co-infected patients. AIDS 21:1855-65

Meyers, Jennifer Hartt; Justement, J Shawn; Hallahan, Claire W et al. (2007) Impact of HIV on cell survival and antiviral activity of plasmacytoid dendritic cells. PLoS ONE 2:e458

Malaspina, Angela; Moir, Susan; Chaitt, Doreen G et al. (2007) Idiopathic CD4+ T lymphocytopenia is associated with increases in immature/transitional B cells and serum levels of IL-7. Blood 109:2086-8

Kottilil, Shyam; Jackson, Julia O; Reitano, Kristin N et al. (2007) Innate immunity in HIV infection: enhanced susceptibility to CD95-mediated natural killer cell death and turnover induced by HIV viremia. J Acquir Immune Defic Syndr 46:151-9