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Altered Monocyte Phenotype in HIV-1 Infection Tends to Normalize with Integrase-Inhibitor-Based Antiretroviral Therapy.

McCausland MR, Juchnowski SM, Zidar DA, Kuritzkes DR, Andrade A, Sieg SF, Lederman MM, Funderburg NT - PLoS ONE (2015)

Bottom Line: Monocytes are increasingly implicated in the inflammatory consequences of HIV-1 disease, yet their phenotype following antiretroviral therapy (ART) initiation is incompletely defined.We also report lower expression of CX3CR1 (p = 0.014) on patrolling monocytes at baseline, compared to levels seen in controls.In HIV-1 infected patients, ART appears to attenuate the high levels of activation (HLA-DR, CD86) and to increase expression of the chemokine receptors CCR2 and CX3CR1 on monocyte populations.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Disease, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.

ABSTRACT

Background: Monocytes are increasingly implicated in the inflammatory consequences of HIV-1 disease, yet their phenotype following antiretroviral therapy (ART) initiation is incompletely defined. Here, we define more completely monocyte phenotype both prior to ART initiation and during 48 weeks of ART.

Methods: Cryopreserved peripheral blood mononuclear cells (PBMCs) were obtained at baseline (prior to ART initiation) and at weeks 12, 24, and 48 of treatment from 29 patients participating in ACTG clinical trial A5248, an open label study of raltegravir/emtricitibine/tenofovir administration. For comparison, cryopreserved PBMCs were obtained from 15 HIV-1 uninfected donors, each of whom had at least two cardiovascular risk factors. Thawed samples were stained for monocyte subset markers (CD14 and CD16), HLA-DR, CCR2, CX3CR1, CD86, CD83, CD40, CD38, CD36, CD13, and CD163 and examined using flow cytometry.

Results: In untreated HIV-1 infection there were perturbations in monocyte subset phenotypes, chiefly a higher frequency and density (mean fluorescence intensity-MFI) of HLA-DR (%-p = 0.004, MFI-p = .0005) and CD86 (%-p = 0.012, MFI-p = 0.005) expression and lower frequency of CCR2 (p = 0.0002) expression on all monocytes, lower CCR2 density on inflammatory monocytes (p = 0.045) when compared to the expression and density of these markers in controls' monocytes. We also report lower expression of CX3CR1 (p = 0.014) on patrolling monocytes at baseline, compared to levels seen in controls. After ART, these perturbations tended to improve, with decreasing expression and density of HLA-DR and CD86, increasing CCR2 density on inflammatory monocytes, and increasing expression and density of CX3CR1 on patrolling monocytes.

Conclusions: In HIV-1 infected patients, ART appears to attenuate the high levels of activation (HLA-DR, CD86) and to increase expression of the chemokine receptors CCR2 and CX3CR1 on monocyte populations. Circulating monocyte phenotypes are altered in untreated infection and tend to normalize with ART; the role of these cells in the inflammatory environment of HIV-1 infection warrants further study.

No MeSH data available.


Related in: MedlinePlus

Monocyte subset proportions at baseline and after ART initiation compared to proportions among controls.(A) Jitterplot comparing the subset proportions in HIV-1-infected individuals prior to ART initiation and subset proportions in controls. Medians are shown, and p values were determined using Mann Whitney U tests. Figs B-D display Tukey boxplots of medians and interquartile ranges. Outliers are shown as open circles. Tukey boxplots show the proportions of traditional monocytes (B), inflammatory monocytes (C) and patrolling monocytes (D) in controls (red) and in HIV-1-infected subjects at baseline and over the course of 48 weeks of ART.
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pone.0139474.g002: Monocyte subset proportions at baseline and after ART initiation compared to proportions among controls.(A) Jitterplot comparing the subset proportions in HIV-1-infected individuals prior to ART initiation and subset proportions in controls. Medians are shown, and p values were determined using Mann Whitney U tests. Figs B-D display Tukey boxplots of medians and interquartile ranges. Outliers are shown as open circles. Tukey boxplots show the proportions of traditional monocytes (B), inflammatory monocytes (C) and patrolling monocytes (D) in controls (red) and in HIV-1-infected subjects at baseline and over the course of 48 weeks of ART.

Mentions: In earlier work using fresh whole blood samples, we found lower proportions of traditional monocytes, and increased proportions of inflammatory and patrolling monocytes in HIV-1 infected patients with uncontrolled viremia [1]. Our new data evaluating a smaller number of cryopreserved samples from different patient and control populations are similar. The proportion of traditional (CD14+CD16-) monocytes tended to be lower in HIV-1-infectedpatients (median-76.6%) compared to the proportion of traditional monocytes among control subjects (median-82.5%), though not significantly lower (p = .089). The proportion of inflammatory (CD14+CD16+) monocytes also tended to be higher in the setting of HIV-1 infection (median-14.8%) than among controls (median-13.9%), though not significantly (p = 0.19). The proportion of patrolling (CD14dimCD16+) monocytes was significantly higher in HIV-1 infection (median-6.0%) than among controls (median-2.9%, p = .029, Fig 2A). These subset proportions did not change with ART (Fig 2B–2D).


Altered Monocyte Phenotype in HIV-1 Infection Tends to Normalize with Integrase-Inhibitor-Based Antiretroviral Therapy.

McCausland MR, Juchnowski SM, Zidar DA, Kuritzkes DR, Andrade A, Sieg SF, Lederman MM, Funderburg NT - PLoS ONE (2015)

Monocyte subset proportions at baseline and after ART initiation compared to proportions among controls.(A) Jitterplot comparing the subset proportions in HIV-1-infected individuals prior to ART initiation and subset proportions in controls. Medians are shown, and p values were determined using Mann Whitney U tests. Figs B-D display Tukey boxplots of medians and interquartile ranges. Outliers are shown as open circles. Tukey boxplots show the proportions of traditional monocytes (B), inflammatory monocytes (C) and patrolling monocytes (D) in controls (red) and in HIV-1-infected subjects at baseline and over the course of 48 weeks of ART.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4591977&req=5

pone.0139474.g002: Monocyte subset proportions at baseline and after ART initiation compared to proportions among controls.(A) Jitterplot comparing the subset proportions in HIV-1-infected individuals prior to ART initiation and subset proportions in controls. Medians are shown, and p values were determined using Mann Whitney U tests. Figs B-D display Tukey boxplots of medians and interquartile ranges. Outliers are shown as open circles. Tukey boxplots show the proportions of traditional monocytes (B), inflammatory monocytes (C) and patrolling monocytes (D) in controls (red) and in HIV-1-infected subjects at baseline and over the course of 48 weeks of ART.
Mentions: In earlier work using fresh whole blood samples, we found lower proportions of traditional monocytes, and increased proportions of inflammatory and patrolling monocytes in HIV-1 infected patients with uncontrolled viremia [1]. Our new data evaluating a smaller number of cryopreserved samples from different patient and control populations are similar. The proportion of traditional (CD14+CD16-) monocytes tended to be lower in HIV-1-infectedpatients (median-76.6%) compared to the proportion of traditional monocytes among control subjects (median-82.5%), though not significantly lower (p = .089). The proportion of inflammatory (CD14+CD16+) monocytes also tended to be higher in the setting of HIV-1 infection (median-14.8%) than among controls (median-13.9%), though not significantly (p = 0.19). The proportion of patrolling (CD14dimCD16+) monocytes was significantly higher in HIV-1 infection (median-6.0%) than among controls (median-2.9%, p = .029, Fig 2A). These subset proportions did not change with ART (Fig 2B–2D).

Bottom Line: Monocytes are increasingly implicated in the inflammatory consequences of HIV-1 disease, yet their phenotype following antiretroviral therapy (ART) initiation is incompletely defined.We also report lower expression of CX3CR1 (p = 0.014) on patrolling monocytes at baseline, compared to levels seen in controls.In HIV-1 infected patients, ART appears to attenuate the high levels of activation (HLA-DR, CD86) and to increase expression of the chemokine receptors CCR2 and CX3CR1 on monocyte populations.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Disease, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.

ABSTRACT

Background: Monocytes are increasingly implicated in the inflammatory consequences of HIV-1 disease, yet their phenotype following antiretroviral therapy (ART) initiation is incompletely defined. Here, we define more completely monocyte phenotype both prior to ART initiation and during 48 weeks of ART.

Methods: Cryopreserved peripheral blood mononuclear cells (PBMCs) were obtained at baseline (prior to ART initiation) and at weeks 12, 24, and 48 of treatment from 29 patients participating in ACTG clinical trial A5248, an open label study of raltegravir/emtricitibine/tenofovir administration. For comparison, cryopreserved PBMCs were obtained from 15 HIV-1 uninfected donors, each of whom had at least two cardiovascular risk factors. Thawed samples were stained for monocyte subset markers (CD14 and CD16), HLA-DR, CCR2, CX3CR1, CD86, CD83, CD40, CD38, CD36, CD13, and CD163 and examined using flow cytometry.

Results: In untreated HIV-1 infection there were perturbations in monocyte subset phenotypes, chiefly a higher frequency and density (mean fluorescence intensity-MFI) of HLA-DR (%-p = 0.004, MFI-p = .0005) and CD86 (%-p = 0.012, MFI-p = 0.005) expression and lower frequency of CCR2 (p = 0.0002) expression on all monocytes, lower CCR2 density on inflammatory monocytes (p = 0.045) when compared to the expression and density of these markers in controls' monocytes. We also report lower expression of CX3CR1 (p = 0.014) on patrolling monocytes at baseline, compared to levels seen in controls. After ART, these perturbations tended to improve, with decreasing expression and density of HLA-DR and CD86, increasing CCR2 density on inflammatory monocytes, and increasing expression and density of CX3CR1 on patrolling monocytes.

Conclusions: In HIV-1 infected patients, ART appears to attenuate the high levels of activation (HLA-DR, CD86) and to increase expression of the chemokine receptors CCR2 and CX3CR1 on monocyte populations. Circulating monocyte phenotypes are altered in untreated infection and tend to normalize with ART; the role of these cells in the inflammatory environment of HIV-1 infection warrants further study.

No MeSH data available.


Related in: MedlinePlus