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AIDS. 2012 Mar 13;26(5):533-41. doi: 10.1097/QAD.0b013e32834f3167.

Differential regulation of toll-like receptor pathways in acute and chronic HIV-1 infection.

Author information

1
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute Technology and Harvard, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA.

Abstract

OBJECTIVE AND DESIGN:

The objective of this study was to determine changes in toll-like receptor (TLR) responses of monocytes, myeloid dendritic cells and plasmacytoid dendritic cells during primary and chronic HIV-1 infection. TLRs serve as important innate receptors to sense pathogens, and have been implicated in mediating immune activation in HIV-1 infection. Studies assessing the consequences of HIV-1 infection on the ability of innate immune cells to respond to TLR stimulation have come to varying conclusions.

METHODS:

Using intracellular flow cytometry, cytokine production by cryopreserved peripheral blood mononuclear cells from healthy controls and HIV-1-infected individuals were examined after TLR stimulation.

RESULTS:

We observed that the effect of HIV-1 infection on TLR responses not only depended on the stage of HIV-1 infection, but was also dependent on the individual receptor and cell type examined. Monocyte and myeloid dendritic cell responses to TLR8 stimulation were associated with HIV-1 viral load and CD4 T-cell count, whereas plasmacytoid dendritic cell responses to TLR7 stimulation were not. Responses to TLR2 stimulation were not affected by HIV-1 infection, whereas responses to TLR9 stimulation were universally decreased in all HIV-1-infected individuals examined regardless of treatment or clinical parameters.

CONCLUSION:

Responsiveness to TLR7/8 stimulation, which have been shown to recognize HIV-1 ssRNA, did not decrease in chronic infection, and may represent a contributing factor to ongoing T-cell immune activation in the setting of chronic viremic HIV-1 infection.

PMID:
22210629
PMCID:
PMC3738004
DOI:
10.1097/QAD.0b013e32834f3167
[Indexed for MEDLINE]
Free PMC Article

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