Maraviroc contributes to the restoration of the homeostasis of regulatory T-cell subsets in antiretroviral-naive HIV-infected subjects

Pozo-Balado, María Mar; Rosado‐Sánchez, Isaac; Méndez-Lagares, Gema; Rodríguez-Méndez, María Mar; Ruiz‐Mateos, Ezequiel; Benhnia, Mohammed Rafii-El-Idrissi; Muñoz‐Fernández, María Ángeles; Leal, Manuel; Pacheco, Yolanda M.

doi:10.1016/j.cmi.2015.12.025

Cited by 12 publications

(8 citation statements)

References 20 publications

(40 reference statements)

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“…Th3 cells may play a role in maintaining Tregs, and may also contribute to the local induction of iTregs [86]. Finally, different Treg subsets may also be distinguished by their different levels of CCR5 expression [87] but at least a subset of these cells are clearly targets for SIV/HIV infection.…”

Section: Specific Cd4+ T Cells Depleted In Siv/hiv Infectionmentioning

confidence: 99%

Intestinal CD4 Depletion in HIV / SIV Infection

Veazey

2019

CIR

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Among the most significant findings in the pathogenesis of HIV infection was the discovery that almost total depletion of intestinal CD4+ T cells occurs rapidly after SIV or HIV infection, regardless of the route of exposure, and long before CD4+ T cell losses occur in blood or lymph nodes. Since these seminal discoveries, we have learned much about mucosal and systemic CD4+ T cells, and found several key differences between the circulating and intestinal CD4+ T cell subsets, both in phenotype, relative proportions, and functional capabilities. Further, specific subsets of CD4+ T cells are selectively targeted and eliminated first, especially cells critically important for initiating primary immune responses, and for maintenance of mucosal integrity (Th1, Th17, and Th22 cells). This simultaneously results in loss of innate immune responses, and loss of mucosal integrity, resulting in mucosal, and systemic immune activation that drives proliferation and activation of new target cells throughout the course of infection. The propensity for the SIV/HIV to infect and efficiently replicate in specific cells also permits viral persistence, as the mucosal and systemic activation that ensues continues to damage mucosal barriers, resulting in continued influx of target cells to maintain viral replication. Finally, infection and elimination of recently activated and proliferating CD4+ T cells, and infection and dysregulation of Tfh and other key CD4+ T cell results in hyperactive, yet non-protective immune responses that support active viral replication and evolution, and thus persistence in host tissue reservoirs, all of which continue to challenge our efforts to design effective vaccine or cure strategies.

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Section: Specific Cd4+ T Cells Depleted In Siv/hiv Infectionmentioning

confidence: 99%

Intestinal CD4 Depletion in HIV / SIV Infection

Veazey

2019

CIR

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“…Maraviroc is a CCR5 receptor antagonist, which is often used clinically in the treatment of HIV infections [ 23 ]. Previous studies have shown that maraviroc can inhibit lipopolysaccharide-induced proinflammatory cytokine expression in human adipocytes [ 24 ], formyl-methionyl-leucyl-phenylalanine-induced chemotactic activity of innate immune cells [ 25 ], and vascular cell adhesion molecule-1 levels in HIV-infected patients [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Maraviroc-Mediated Lung Protection following Trauma-Hemorrhagic Shock

Liu

Zheng

2016

BioMed Research International

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Objectives. The peroxisome proliferator-activated receptor gamma (PPARγ) pathway exerts anti-inflammatory effects in response to injury. Maraviroc has been shown to have potent anti-inflammatory effects. The aim of this study was to investigate whether PPARγ plays an important role in maraviroc-mediated lung protection following trauma-hemorrhage. Methods. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35–40 mmHg for 90 minutes), followed by fluid resuscitation. During resuscitation, a single dose of maraviroc (3 mg/kg, intravenously) with and without a PPARγ inhibitor GW9662 (1 mg/kg, intravenously), GW9662, or vehicle was administered. Lung water content, tissue histology, and other various parameters were measured (n = 8 rats/group) 24 hours after resuscitation. One-way ANOVA and Tukey's testing were used for statistical analysis. Results. Trauma-hemorrhage significantly increased lung water content, myeloperoxidase activity, intercellular adhesion molecule-1, interleukin-6, and interleukin-1β levels. These parameters significantly improved in the maraviroc-treated rats subjected to trauma-hemorrhage. Maraviroc treatment also decreased lung tissue damage as compared to the vehicle-treated trauma-hemorrhaged rats. Coadministration of GW9662 with maraviroc abolished the maraviroc-induced beneficial effects on these parameters and lung injury. Conclusion. These results suggest that PPARγ might play a key role in maraviroc-mediated lung protection following trauma-hemorrhage.

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“…In two clinical trials, an improvement of duodenal immunity and a reduction in bone loss has been associated with such combinations [ 9 , 10 ]. Furthermore, MVC monotherapy also reduced the frequency of regulatory T-cells (Treg) in antiretroviral-naïve subjects [ 11 ], even improving the distribution of Treg subsets [ 12 ]. This could be relevant since we observed that Treg cells negatively impacted the HBV vaccine responsiveness in a previous cohort [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Improved CD4 T cell profile in HIV-infected subjects on maraviroc-containing therapy is associated with better responsiveness to HBV vaccination

et al. 2018

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BackgroundMaraviroc-containing combined antiretroviral therapy (MVC-cART) improved the response to the hepatitis B virus (HBV) vaccine in HIV-infected subjects younger than 50 years old. We aimed here to explore the effect of this antiretroviral therapy on different immunological parameters that could account for this effect.MethodsWe analysed baseline samples of vaccinated subjects under 50 years old (n = 41). We characterized the maturational subsets and the expression of activation, senescence and prone-to-apoptosis markers on CD4 T-cells; we also quantified T-regulatory cells (Treg) and dendritic cell (DC) subsets. We used binary logistic regression to evaluate the immunological impact of MVC-cART, correlation with MVC exposure and linear regression for association with the magnitude of the HBV vaccine response.ResultsHIV-infected subjects on MVC-cART prior to vaccination showed increased recent thymic emigrants levels and reduced myeloid-DC levels. A longer exposure to MVC-cART was associated with lower frequencies of Tregs and activated and proliferating CD4 T-cells. Furthermore, the frequencies of activated and proliferating CD4 T-cells were inversely associated with the magnitude of the HBV vaccine response.ConclusionThe beneficial effect of MVC-cART in the HBV vaccine response in subjects below 50 years old could be partially mediated by its reducing effect on the frequencies of activated and proliferating CD4 T-cells prior to vaccination.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1617-1) contains supplementary material, which is available to authorized users.

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Maraviroc contributes to the restoration of the homeostasis of regulatory T-cell subsets in antiretroviral-naive HIV-infected subjects

Cited by 12 publications

References 20 publications

Intestinal CD4 Depletion in HIV / SIV Infection

Intestinal CD4 Depletion in HIV / SIV Infection

Maraviroc-Mediated Lung Protection following Trauma-Hemorrhagic Shock

Improved CD4 T cell profile in HIV-infected subjects on maraviroc-containing therapy is associated with better responsiveness to HBV vaccination

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