A role for TLR signaling during B cell activation in antiretroviral-treated HIV individuals

Basile Siewe, Ali Keshavarzian, Audrey French, Patricia Demarais, Alan Landay

Research output: Contribution to journalArticlepeer-review


The mechanisms underlying B cell activation that persists during antiretroviral therapy (ART) are unknown. Toll-like receptor (TLR) signaling is a critical mediator of innate cell activation and though B cells express TLRs, few studies have investigated a role for TLR signaling in B cell activation during HIV infection. We addressed this question by assessing the activated phenotype and TLR expression/responsiveness of B cells from ART-treated HIV-infected subjects (HIVART+). We evaluated activation markers implicated in B cell-mediated T cell trans infection during HIV pathogenesis. We found no significant difference in TLR expression between B cells of HIVART+ and HIV- subjects. However, B cells of HIVART+ subjects exhibited heightened endogenous expression levels of IL-6 (p=0.0051), T cell cognate ligands CD40 (p=0.0475), CD54 (p=0.0229), and phosphorylated p38 (p<0.0001), a marker of TLR signaling. In vitro, B cells of HIVART+ individuals were less responsive to TLR stimulation compared to B cells of HIV- subjects. The activated phenotype of in vitro TLR-stimulated B cells of HIV - subjects was similar to ex vivo B cells from HIVART + individuals. TLR2 stimulation was a potent mediator of B cell activation, whereas B cells were least responsive to TLR4 stimulation. Compared to HIV- subjects, the serum level of lipoteichoic acid (TLR2 ligand) in HIVART+ subjects was significantly higher (p=0.0207), correlating positively with viral load (p=0.0127, r=0.6453). Our data suggest that during HIV infection TLR-activated B cells may exert a pathogenic role and B cells from HIVART+ subjects respond to in vitro TLR stimulation, yet exhibit a TLR tolerant phenotype suggesting prior in vivo TLR stimulation.

Original languageEnglish (US)
Pages (from-to)1353-1360
Number of pages8
JournalAIDS Research and Human Retroviruses
Issue number10
StatePublished - Oct 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases


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