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

J. Judy Chang, Aurore Lacas, Robert J. Lindsay, Erin H. Doyle, Karen L. Axten, Florencia Pereyra, Eric S. Rosenberg, Bruce D. Walker, Todd M. Allen, Marcus Altfeld

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


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.

Original languageEnglish
Pages (from-to)533-541
Number of pages9
Issue number5
StatePublished - 4 Jan 2012
Externally publishedYes


  • Dendritic cells
  • HIV-1
  • Innate immunity
  • Monocytes
  • Pathogenesis
  • Toll-like receptor


Dive into the research topics of 'Differential regulation of toll-like receptor pathways in acute and chronic HIV-1 infection'. Together they form a unique fingerprint.

Cite this