title: Endotoxemia is associated with altered innate and adaptive immune responses in untreated HIV-1 infected individuals.
abstract: BACKGROUND
  Microbial translocation may contribute to the immunopathogenesis in HIV infection. We investigated if microbial translocation and inflammation were associated with innate and adaptive immune responses in adults with HIV.
  
  
  RESULTS
  This was an observational cohort study. Sera from HIV-infected and HIV-uninfected individuals were analyzed for microbial translocation (soluble CD14, lipopolysaccharides [LPS], endotoxin core antibody, and anti-α-galactosyl antibodies) and inflammatory markers (high sensitivity C-reactive protein, IL-6, IL-1 receptor antagonist, soluble tumor necrosis factor receptor II, and IL-10) with enzyme-linked immunosorbent assays. Peripheral blood mononuclear cells (PBMC) from HIV-infected persons and healthy controls (primed with single-stranded HIV-1-derived RNA) were stimulated with LPS, and cytokine production was measured. Finally, HIV-infected patients were immunized with Prevnar 7vPnC±CpG 7909 followed by Pneumo Novum PPV-23. Effects of microbial translocation and inflammation on immunization were analyzed in a predictive regression model. We included 96 HIV-infected individuals, 76 on highly active antiretroviral therapy (HAART), 20 HAART-naive, and 50 healthy controls. Microbial translocation and inflammatory markers were higher among HIV-infected persons than controls. Cytokine levels following LPS stimulation were increased in PBMCs from HAART-naive compared to HAART-treated HIV-infected persons. Further, RNA-priming of PBMCs from controls acted synergistically with LPS to augment cytokine responses. Finally, high serum LPS levels predicted poor vaccine responses among HAART-naive, but not among HAART-treated HIV-infected individuals.
  
  
  CONCLUSIONS
  LPS acts synergistically with HIV RNA to stimulate innate immune responses in vitro and increasing serum LPS levels seem to predict poor antibody responses after vaccination among HAART-naive HIV-infected persons. Thus, our results suggest that microbial translocation may be associated with innate and adaptive immune dysfunction in untreated HIV infection.
authors: Department of Infectious Diseases, Aarhus University Hospital Skejby, Aarhus, Denmark. arbukh@gmail.com
authors: Anne Roslev
authors: AR
authors: Bukh
authors: Jesper
authors: J
authors: Melchjorsen
authors: Rasmus
authors: R
authors: Offersen
authors: Jens Magnus Bernth
authors: JM
authors: Jensen
authors: Lars
authors: L
authors: Toft
authors: Henrik
authors: H
authors: Støvring
authors: Lars
authors: L
authors: Ostergaard
authors: Martin
authors: M
authors: Tolstrup
authors: Ole Schmeltz
authors: OS
authors: Søgaard
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D019446:Endotoxemia / Q000150:complications* / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000097:blood / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000378:metabolism; D014611:Vaccination
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D012367:RNA, Viral