Enhanced immune activation linked to endotoxemia in HIV-1 seronegative MSM

Palmer, Christine D.; Tomassilli, Julia C.; Sirignano, Michael; Romero-Tejeda, Marisol; Arnold, Kelly B.; Che, Denise; Lauffenburger, Douglas A.; Jost, Stéphanie; Allen, Todd M.; Mayer, Kenneth H.; Altfeld, Marcus

doi:10.1097/qad.0000000000000386

Cited by 29 publications

(37 citation statements)

References 20 publications

(18 reference statements)

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“…PBMCs were stained with antibody panels testing for T cell activation [33] and monocyte/DC characteristics [34] as previously described. Details of antibodies and stains used in each panel are listed in Supplementary File 1.…”

Section: Methodsmentioning

confidence: 99%

Increased frequencies of CD8⁺CD57⁺ T cells are associated with antibody neutralization breadth against HIV in viraemic controllers

Palmer

Romero-Tejeda

Scully

et al. 2016

Journal of the International AIDS Society

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IntroductionAn effective prophylactic vaccine against HIV will need to elicit antibody responses capable of recognizing and neutralizing rapidly evolving antigenic regions. The immunologic milieu associated with development of neutralizing antibody breadth remains to be fully defined. In this study, we sought to identify immunological signatures associated with neutralization breadth in HIV controllers. We applied an immune monitoring approach to analyze markers of T cell and myeloid cell activation by flow cytometry, comparing broad neutralizers with low- and non-neutralizers using multivariate and univariate analyses.MethodsAntibody neutralization breadth was determined, and cryopreserved peripheral blood mononuclear cells were stained for T cell and myeloid cell activation markers. Subjects were grouped according to neutralization breadth, and T cell and myeloid cell activation was analyzed by partial least squares discriminant analysis to determine immune signatures associated with high neutralization breadth.ResultsWe show that neutralization breadth in HIV viraemic controllers (VC) was strongly associated with increased frequencies of CD8+CD57+ T cells and that this association was independent of viral load, CD4 count and time since HIV diagnosis.ConclusionsOur data show elevated frequencies of CD8+CD57+ T cells in VC who develop neutralization breadth against HIV. This immune signature could serve as a potential biomarker of neutralization breadth and should be further investigated in other HIV-positive cohorts and in HIV vaccine trials.

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Section: Methodsmentioning

confidence: 99%

Increased frequencies of CD8⁺CD57⁺ T cells are associated with antibody neutralization breadth against HIV in viraemic controllers

Palmer

Romero-Tejeda

Scully

et al. 2016

Journal of the International AIDS Society

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“…We recently reported a high incidence of subclinical endotoxemia in a cohort of HIV negative men (20). Endotoxin levels detected in this particular cohort were comparable to those observed in HIV-positive individuals (Supplemental Figure S1), making this study population ideal for modeling in vivo effects of subclinical endotoxemia on immune cell function in the absence of HIV infection and associated viral effects.…”

Section: Resultsmentioning

confidence: 99%

“…We previously reported on a cohort of HIV negative men with subclinical endotoxemia that correlated with decreased CD4/CD8 T cell ratio, elevated plasma cytokine levels and markers of T cell exhaustion (20). Using this HIV negative population as an in vivo model of subclinical endotoxemia in the absence of confounding HIV infection and associated viral effects, we assessed the effects of subclinical endotoxemia on cellular immune functions ex vivo .…”

Section: Introductionmentioning

confidence: 99%

Naturally Occurring Subclinical Endotoxemia in Humans Alters Adaptive and Innate Immune Functions through Reduced MAPK and Increased STAT1 Phosphorylation

Palmer

Romero-Tejeda

Sirignano

et al. 2016

The Journal of Immunology

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Multiple studies have shown correlates of immune activation with microbial translocation and plasma LPS during HIV infection. It is unclear whether this activation is due to LPS, residual viral replication, or both. Few studies have addressed the effects of persistent in vivo levels of LPS on specific immune functions in humans in the absence of chronic viral infection or pathological settings such as sepsis. We previously reported on a cohort of HIV negative men with subclinical endotoxemia linked to alterations in CD4/CD8 T cell ratio and plasma cytokine levels. This HIV negative cohort allowed us to assess cellular immune functions in the context of different subclinical plasma LPS levels ex vivo without confounding viral effects. By comparing 2 samples of differing plasma LPS levels from each individual, we now show that subclinical levels of plasma LPS in vivo significantly alter T cell proliferative capacity, monocyte cytokine release and HLA-DR expression, and induce TLR cross-tolerance by decreased phosphorylation of MAPK pathway components. Using this human in vivo model of subclinical endotoxemia, we furthermore show that plasma LPS leads to constitutive activation of STAT1 through autocrine cytokine signaling, suggesting that subclinical endotoxemia in healthy individuals might lead to significant changes in immune function that have thus far not been appreciated.

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“…Compared to people living with HIV (PLHIV), similar or lower levels of IA were reported in HESN [14] [15] [16] [17]. Compared to HIV-neg Controls, some studies reported higher levels of IA in HESN [11] [16] [18] [19] while others reported lower levels [20]- [25], To gain further insight into IA in serodiscordant couples, we aimed to compare the levels (using beta 2 microglobulin (β 2 m) as a soluble marker of IA) between HESN, their HIV+ counterparts and HIV-neg Controls; then analyze the association of IA levels and sexual exposure to HIV (SEHIV).…”

Section: Introductionmentioning

confidence: 99%

Chronic Immune Activation and Sexual Exposure among HIV Serodiscordant Couples in Senegal

Diouf¹,

Trottier²,

Mbow³

et al. 2019

AID

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Retraction type (multiple responses allowed):  Unreliable findings   Lab error  Inconsistent data  Analytical error  Biased interpretation   Other:  Irreproducible results  Failure to disclose a major competing interest likely to influence interpretations or recommendations  Unethical research   Fraud   Data fabrication  Fake publication  Other:  Plagiarism  Self plagiarism  Overlap  Redundant publication *  Copyright infringement  Other legal concern:  Editorial reasons   Handling error  Unreliable review(s)  Decision error  Other: X Other: AID does not meet author's publication requirements Results of publication (only one response allowed): Xare still valid.  were found to be overall invalid. Author's conduct (only one response allowed):  honest error  academic misconduct Xnone (not applicable in this casee.g. in case of editorial reasons) * Also called duplicate or repetitive publication. Definition: "Publishing or attempting to publish substantially the same work more than once." History Expression of Concern:  yes, date: yyyy-mm-dd Xno Correction:  yes, date: yyyy-mm-dd Xno Comment: AID does not meet author's publication requirements This article has been retracted to straighten the academic record. In making this decision the Editorial Board follows COPE's Retraction Guidelines. Aim is to promote the circulation of scientific research by offering an ideal research publication platform with due consideration of internationally accepted standards on publication ethics. The Editorial Board would like to extend its sincere apologies for any inconvenience this retraction may have caused.

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Enhanced immune activation linked to endotoxemia in HIV-1 seronegative MSM

Cited by 29 publications

References 20 publications

Increased frequencies of CD8⁺CD57⁺ T cells are associated with antibody neutralization breadth against HIV in viraemic controllers

Increased frequencies of CD8⁺CD57⁺ T cells are associated with antibody neutralization breadth against HIV in viraemic controllers

Naturally Occurring Subclinical Endotoxemia in Humans Alters Adaptive and Innate Immune Functions through Reduced MAPK and Increased STAT1 Phosphorylation

Chronic Immune Activation and Sexual Exposure among HIV Serodiscordant Couples in Senegal

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Enhanced immune activation linked to endotoxemia in HIV-1 seronegative MSM

Cited by 29 publications

References 20 publications

Increased frequencies of CD8+CD57+ T cells are associated with antibody neutralization breadth against HIV in viraemic controllers

Increased frequencies of CD8+CD57+ T cells are associated with antibody neutralization breadth against HIV in viraemic controllers

Naturally Occurring Subclinical Endotoxemia in Humans Alters Adaptive and Innate Immune Functions through Reduced MAPK and Increased STAT1 Phosphorylation

Chronic Immune Activation and Sexual Exposure among HIV Serodiscordant Couples in Senegal

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Increased frequencies of CD8⁺CD57⁺ T cells are associated with antibody neutralization breadth against HIV in viraemic controllers

Increased frequencies of CD8⁺CD57⁺ T cells are associated with antibody neutralization breadth against HIV in viraemic controllers