Dataset Information

Endotoxemia is associated with altered innate and adaptive immune responses in untreated HIV-1 infected individuals.

ABSTRACT: 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.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-?-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.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.

SUBMITTER: Bukh AR

PROVIDER: S-EPMC3123300 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Endotoxemia is associated with altered innate and adaptive immune responses in untreated HIV-1 infected individuals.

Bukh Anne Roslev AR Melchjorsen Jesper J Offersen Rasmus R Jensen Jens Magnus Bernth JM Toft Lars L Støvring Henrik H Ostergaard Lars L Tolstrup Martin M Søgaard Ole Schmeltz OS

PloS one 20110624 6

<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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-galactos ...[more]

PMID: 21731690

Similar Datasets

Project description:BackgroundAlthough gut microbiota dysbiosis has been reported in HIV infected individuals recently, the relationship between the gut microbiota and immune activation in patients with different immune responses to highly active antiretroviral therapy (HAART) is still not well understood. Gut microbiota and immune activation were studied in 36 non-HIV-infected subjects (healthy controls) and 58 HIV-infected individuals, including 28 immunological responders (IR) and 30 immunological non-responders (INR) (≥500 and < 200 CD4+ T-cell counts/μl after 2 years of HIV-1 viral suppression respectively) without comorbidities.ResultsMetagenome sequencing revealed that HIV-infected immunological responders and immunological non-responders could not recover completely from the gut microbiota dysbiosis. At a 97% similarity level, the relative abundances of Fusobacterium, Ruminococcus gnavus and Megamonas were greater, whereas Faecalibacterium, Alistipes, Bifidobacterium, Eubacterium rectale and Roseburia were more depleted in the IR and INR groups than those in the healthy controls. Ruminococcaceae and Alistipes were positively correlated with nadir and current CD4+ T-cell counts, but negatively correlated with CD8 + CD57+ T-cell counts. Inflammation markers and translocation biomarkers (LPS) levels were positively correlated with the abundances of genera Ruminococcus and Fusobacterium but were negatively correlated with the genus Faecalibacterium. The relative abundances of Escherichia-Shigella and Blautia were significantly higher in the IR than those in the INR group. Escherichia-Shigella were negatively correlated with the CD4/CD8 ratio but positively correlated with the amount of CD8 + CD57+ T-cells. Roseburia and Blautia were negatively associated with nadir CD4+ T-cell and positively associated with CD8 + CD57+ T-cell counts.ConclusionsGut microbiota dysbiosis may be one of the factors contributing to different immune responses and treatment outcomes to HAART.

Project description:The sharp increase in the proportion of asymptomatic cases and the potential risk of virus transmission have greatly increased the difficulty of controlling the COVID-19 pandemic. The individual immune response is closely associated with clinical outcomes and pathogenic mechanisms of COVID-19. However, the clinical characteristics and immunophenotyping features of immune cells of asymptomatic individuals remain somewhat mysterious. To better understand and predict the disease state and progress, we performed a comprehensive analysis of clinical data, laboratory indexes and immunophenotyping features in 41 patients with SARS-CoV-2 (including 24 asymptomatic cases and 17 symptomatic individuals). Firstly, from the perspective of demographic characteristics, the rate of asymptomatic infection was significantly higher in those with younger age. Secondly, the laboratory test results showed that some indexes, such as CRP (acute phase reaction protein), D-Dimer and fibrinogen (the marker for coagulation) were lower in the asymptomatic group. Finally, symptomatic individuals were prone to establishing a non-protective immune phenotype by abnormally decreasing the lymphocyte count and percentage, abnormally increasing the Th17 percentage and decreasing Treg percentage, which therefore cause an increase in the neutrophil/lymphocyte ratio (NLR), monocytes/lymphocytes ratio (MLR) and Th17/Treg ratio. On the other hand, asymptomatic individuals tended to establish a more effective and protective immune phenotype by maintaining a normal level of lymphocyte count and percentage and a high level of NK cells. At the same time, asymptomatic individuals can establish a relatively balanced immune response through maintaining a low level of monocytes, a relatively low level of Th17 and high level of Treg, which therefore lead to a decrease in MNKR and Th17/Treg ratio and finally the avoidance of excessive inflammatory responses. This may be one of the reasons for their asymptomatic states. This study is helpful to reveal the immunological characteristics of asymptomatic individuals, understand immune pathogenesis of COVID-19 and predict clinical outcomes more precisely. However, owing to small sample sizes, a future study with larger sample size is still warranted.

Dataset Information

Endotoxemia is associated with altered innate and adaptive immune responses in untreated HIV-1 infected individuals.

Publications

Endotoxemia is associated with altered innate and adaptive immune responses in untreated HIV-1 infected individuals.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets