Defective plasmacytoid dendritic cell-NK cell cross-talk in HIV infection.
HIV viremia is associated with a wide range of immune dysfunctions that contribute to the immunocompromised state. HIV viremia has been shown to have a broad effect on several immune cell types and/or their interactions that are vital for mounting an effective immune response. In this study, we investigated the integrity of plasmacytoid dendritic cell (pDC)-NK cell interactions among HIV viremic, aviremic, and seronegative individuals. We describe a critical defect in the ability of pDCs from HIV-infected individuals to secrete IFN-alpha and TNF and subsequently activate NK cells. We also describe an inherent defect on 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 the HIV gp120-mediated suppressive effect on NK cells was a result of its binding to the integrin alpha(4)beta(7) expressed on NK cells. These findings suggest a novel mechanism by which HIV is capable of suppressing an innate immune function in infected individuals.
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health/DHHS, SAIC-Frederick, NCI, Frederick, MD 21702, USA.
K N
KN
Reitano
S
S
Kottilil
C M
CM
Gille
X
X
Zhang
M
M
Yan
M A
MA
O'Shea
G
G
Roby
C W
CW
Hallahan
J
J
Yang
R A
RA
Lempicki
J
J
Arthos
A S
AS
Fauci
D003713:Dendritic Cells / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D016898:Interferon-alpha / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D011485:Protein Binding; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014766:Viremia / Q000276:immunology
D015699:HIV Envelope Protein gp120; D016023:Integrins; D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha; C071777:integrin alpha4beta7