title: R-848 triggers the expression of TLR7/8 and suppresses HIV replication in monocytes.
abstract: BACKGROUND
  Toll-like receptors (TLR) 7 and 8 are important in single-stranded viral RNA recognition and may play a role in HIV infection and disease progression. We analyzed TLR7/8 expression and signaling in monocytes from HIV-infected and uninfected subjects to investigate a pathway with new potential for the suppression of HIV replication.
  
  
  METHODS
  Eighty-one HIV-infected and uninfected subjects from Liaoning and Henan provinces in China participated in this study. Monocytes were isolated from subjects' peripheral blood mononuclear cells by magnetic bead selection. TLR7 and TLR8 mRNA was measured using quantitative real-time reverse transcriptase PCR. R-848 (resiquimod) was used as a ligand for TLR7 and TLR8 in order to 1) assess TLR7/8-mediated monocyte responsiveness as indicated by IL-12 p40 and TNF-α secretion and 2) to examine HIV replication in cultured monocytes in the presence of R-848.
  
  
  RESULTS
  We found that expression of TLR7/8 mRNA in peripheral blood monocytes decreased with disease progression. TLR7 expression was decreased with stimulation with the TLR7/8 agonist, R-848, in vitro, whereas TLR8 expression was unaffected. Following R-848 stimulation, monocytes from HIV-infected subjects produced significantly less TNF-α than those from uninfected subjects, but trended towards greater production of IL-12 than stimulated monocytes from uninfected subjects. R-848 stimulation also suppressed HIV replication in cultured monocytes.
  
  
  CONCLUSIONS
  Our study provides evidence that the TLR7 and TLR8 triggering can suppress HIV replication in monocytes and lead to postpone HIV disease progression, thereby offering novel targets for immunomodulatory therapy.
authors.affiliation: Key Laboratory of AIDS Immunology of Ministry of Health, Department of Laboratory Medicine, No 1 Hospital of China Medical University, No 155 Nanjing North Street, Heping District, Shenyang 110001, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Nian
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Geng
authors.forename: Hua-Lu
authors.initials: HL
authors.lastname: Cui
authors.forename: Ming-jia
authors.initials: MJ
authors.lastname: Bao
authors.forename: Zi-ning
authors.initials: ZN
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Pan
authors.forename: Qing-Hai
authors.initials: QH
authors.lastname: Hu
authors.forename: Hong
authors.initials: H
authors.lastname: Shang
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D002681:China; D005260:Female; D020869:Gene Expression Profiling; D006678:HIV / Q000254:growth & development* / Q000276:immunology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000821:virology*; D051199:Toll-Like Receptor 7 / Q000096:biosynthesis* / Q000276:immunology; D051200:Toll-Like Receptor 8 / Q000096:biosynthesis* / Q000276:immunology; D014779:Virus Replication
chemical_list: D007093:Imidazoles; D007155:Immunologic Factors; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; C402365:resiquimod