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. 2011;6(6):e21275.
doi: 10.1371/journal.pone.0021275. Epub 2011 Jun 24.

"VSports手机版" Endotoxemia is associated with altered innate and adaptive immune responses in untreated HIV-1 infected individuals

Anne Roslev Bukh  1 , Jesper Melchjorsen, Rasmus Offersen, Jens Magnus Bernth Jensen, Lars Toft, Henrik Støvring, Lars Ostergaard, Martin Tolstrup, Ole Schmeltz Søgaard
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Endotoxemia is associated with altered innate and adaptive immune responses in untreated HIV-1 infected individuals

Anne Roslev Bukh et al. PLoS One. 2011.

"VSports手机版" 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 VSports手机版. .

Methodology/principal findings: 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 V体育安卓版. 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/significance: 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. V体育ios版.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Microbial translocation in HIV-infected individuals and HIV-uninfected controls.
(A) Median serum level of LPS in our cohort; controls: 1.55 EU/mL, HIV-infected persons: 1.82 EU/mL, p = 0.061. (B) Median serum level of sCD14 in our cohort; controls: 3.18 µg/mL, HIV-infected persons: 7.58 µg/mL, p<0.001. (C) Median serum level of endoCAb in our cohort; controls: 34.6 GMU/mL, HIV-infected persons: 26.2 GMU/mL, p = 0.08. (D) Median serum level of anti-Gal IgM in our cohort; controls: 288.4 AU, HIV-infected persons: 171.2 AU, p = 0.57. (E) Median serum level of anti-Gal IgG in our cohort; controls: 13.38 AU, HIV-infected persons: 9.28 AU, p = 0.14.
Figure 2
Figure 2. PBMC responsiveness to HIV RNA and LPS.
(A) TNF-α stimulation index (SI) in HAART-naive and HAART-treated HIV-infected PBMCs stimulated with LPS (p = 0.03). (B) IFN-α SI in HAART-naive and HAART-treated HIV-infected PBMCs stimulated with LPS (p = 0.002). (C) IFN-γ SI in HAART-naive and HAART-treated HIV-infected PBMCs stimulated with LPS (p = 0.003). (D) TNF-α SI (log10) vs. HIV RNA (log10) in LPS-stimulated HAART-naive HIV-infected PBMCs, p<0.001. (E) Level of TNF-α in healthy PBMCs left untreated or primed with 0.1 µg/mL of ssRNA40 or ssRNA41 (control), and subsequently stimulated with LPS; unprimed vs. 0.1 µg/mL ssRNA in non-stimulated PBMCs, p<0.001, in PBMCs stimulated wth 1 ng/mL LPS, p<0.001, PBMCs stimulated with 10 ng/mL LPS, p<0.001, and PBMCs stimulated with 100 ng/mL LPS, p<0.001. Experiment was performed on PBMCs from four independent donors. Results depicted from one representative stimulation experiment, performed in triplicate.
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