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Title: HIV type 1 infection up-regulates TLR2 and TLR4 expression and function in vivo and in vitro
Author: Hernandez Lopez, Juan Carlos
Stevenson M.
Latz E.
Urcuqui-Inchima S.
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Issue Date: 2012
Keywords: abacavir
B7 antigen
beta actin
CD123 antigen
CD14 antigen
CD4 antigen
immunoglobulin enhancer binding protein
interleukin 1beta
interleukin 6
messenger RNA
toll like receptor 2
toll like receptor 4
tumor necrosis factor alpha
acquired immune deficiency syndrome
CD4+ T lymphocyte
cell subpopulation
clinical article
controlled study
cytokine production
ex vivo study
gene expression regulation
highly active antiretroviral therapy
human cell
Human immunodeficiency virus 1
Human immunodeficiency virus 1 infection
Human immunodeficiency virus infected patient
immune response
in vitro study
in vivo study
innate immunity
myeloid dendritic cell
peripheral blood mononuclear cell
plasmacytoid dendritic cell
Abstract: Toll-like receptors (TLRs) play a critical role in innate immunity against pathogens. Their stimulation induces the activation of NF-?B, an important inducer of HIV-1 replication. In recent years, an increasing number of studies using several cells types from HIV-infected patients indicate that TLRs play a key role in regulating the expression of proinflammatory cytokines and viral pathogenesis. In the present study, the effect of HIV-1 stimulation of monocyte-derived macrophage (MDM) and peripheral blood mononuclear cell (PBMC) subpopulations from healthy donors on the expression and functions of TLR2 and TLR4 was examined. In addition, and to complete the in vitro study, the expression pattern of TLR2 and TLR4 in 49 HIV-1-infected patients, classified according to viral load and the use of HAART, was determined and compared with 25 healthy subjects. An increase of TLR expression and production of proinflammatory cytokines were observed in MDMs and PBMCs infected with HIV-1 in vitro and in response to TLR stimulation, compared to the mock. In addition, an association between TLR expression and up-regulation of CD80 in plasmacytoid dendritic cells (pDCs) was observed. The ex vivo analysis indicated increased expression of TLR2 and TLR4 in myeloid dendritic cells (mDCs), but only of TLR2 in monocytes obtained from HIV-1-infected patients, compared to healthy subjects. Remarkably, the expression was higher in cells from patients who do not use HAART. In monocytes, there was a positive correlation between both TLRs and viral load, but not CD4+ T cell numbers. Together, our in vitro and ex vivo results suggest that TLR expression and function can be up-regulated in response to HIV-1 infection and could affect the inflammatory response. We propose that modulation of TLRs represents a mechanism to promote HIV-1 replication or AIDS progression in HIV-1-infected patients. © 2012, Mary Ann Liebert, Inc.
Type: Artículo
Citation: Hernández JC,Stevenson M,Latz E,Urcuqui S. HIV type 1 infection up-regulates TLR2 and TLR4 expression and function in vivo and in vitro. AIDS Res Hum Retroviruses. 2012. 28. (10):p. 1313-1328. .
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Appears in Collections:Artículos Científicos

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