hiv-1 rna dysregulates the natural tlr response to subclinical endotoxemia in kenyan female sex-workershiv - 1 rna就是说自然tlr应对亚临床内毒素在肯尼亚的女性性工作者.pdfVIP

HIV-1 RNA Dysregulates the Natural TLR Response to Subclinical Endotoxemia in Kenyan Female Sex-Workers 1,2 3 1,4 1 2 5 Richard T. Lester *, Xiao-Dan Yao , T. Blake Ball , Lyle R. McKinnon , Were R. Omange , Rupert Kaul , 2 2 3 1,4 Charles Wachihi , Walter Jaoko , Kenneth L. Rosenthal , Francis A. Plummer 1 Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada, 2 Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya, 3 Department of Pathology Molecular Medicine, McMaster University, Hamilton, Ontario, Canada, 4 National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada, 5 Department of Medicine, University Health Network and University of Toronto, Toronto, Ontario, Canada Abstract Background: Subclinical endotoxemia has been reported in HIV-1 infected persons and may drive systemic immune activation and pathogenesis. Proinflammatory responsiveness to endotoxin (LPS) is mediated by Toll-like receptor 4 (TLR4). We therefore examined the association between plasma LPS levels, HIV RNA, and TLR4 expression and cytokine responses in the blood of HIV infected and uninfected participants in a cohort of female sex-workers in Kenya. Methodology/Principal Findings: Ex vivo plasma and peripheral blood mononuclear cells (PBMC) were assessed for LPS and TLR mRNA, respectively. The effects of HIV single stranded RNA, a TLR8 ligand, on TLR4 and LPS signaling were further assessed in short term PBMC culture. Both HIV uninfected and infected subjects frequently had low detectable LPS levels in thei