PDL1 expression on monocytes is associated with plasma cytokines in Tuberculosis and HIV.

<h4>Introduction</h4>PDL1 and its interaction with PD1 is implicated in immune dysfunction in TB and HIV. The expression of PDL1 on multiple subsets of monocytes as well as their associations with cytokines and microbial products have not been well studied.<h4>Method</h4>HIV...

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Main Authors: Wegene Tamene, Meseret Abebe, Liya Wassie, Helina Mollalign, Katrin Bauer, Amha Kebede, Vincent C Marconi, Rawleigh Howe, Ulrich Sack
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0258122
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author Wegene Tamene
Meseret Abebe
Liya Wassie
Helina Mollalign
Katrin Bauer
Amha Kebede
Vincent C Marconi
Rawleigh Howe
Ulrich Sack
author_facet Wegene Tamene
Meseret Abebe
Liya Wassie
Helina Mollalign
Katrin Bauer
Amha Kebede
Vincent C Marconi
Rawleigh Howe
Ulrich Sack
author_sort Wegene Tamene
collection DOAJ
description <h4>Introduction</h4>PDL1 and its interaction with PD1 is implicated in immune dysfunction in TB and HIV. The expression of PDL1 on multiple subsets of monocytes as well as their associations with cytokines and microbial products have not been well studied.<h4>Method</h4>HIV (TB-HIV+), TB (TB+HIV-) and TB/HIV co-infected (TB+HIV+) patients as well as apparently healthy controls (TB-HIV-) were recruited. TB and HIV patients were treatment naïve while TB/HIV patients were both ART naïve and experienced but not yet started TB therapy. Monocyte subsets were evaluated for PDL1 expression by flow cytometry; plasma TNFα, IL6, IP10, IFNγ and IL10 were measured by Luminex; and cytokine mRNA from purified monocytes quantitated by qPCR. The association of PDL1 with cytokines, clinical and microbial indices, including HIV viral load, TB smear microscopy and TB urinary lipoarabinomannan (LAM) were assessed.<h4>Results</h4>Monocyte expression of PDL1 was significantly higher in TB, HIV and TB/HIV co-infected patients compared with healthy controls (p = 0.0001), with the highest levels in TB/HIV co-infected patients. The highest expression of PDL1 was on intermediate (CD14+CD16+) monocytes in all participant groups. PDL1 strongly correlated with HIV viral load in TB/HIV while weakly correlated in HIV. PDL1 levels moderately correlated with plasma TNFα, IL6, IP10, IFNγ and IL10 level in TB subjects whereas weakly correlated with TNFα and IP10 in HIV patients. However, cytokine mRNA from purified monocytes showed no association with either plasma cytokines or monocyte PDL1 expression, implying that if cytokines modulate PDL1, they are likely not originating from circulating monocytes themselves. These results underscore the importance of further characterization of multiple monocyte subsets and their phenotypic and functional differences in different disease states.
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spelling doaj.art-49f2e9ec56a8490987c612277caebb922022-12-21T22:43:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-011610e025812210.1371/journal.pone.0258122PDL1 expression on monocytes is associated with plasma cytokines in Tuberculosis and HIV.Wegene TameneMeseret AbebeLiya WassieHelina MollalignKatrin BauerAmha KebedeVincent C MarconiRawleigh HoweUlrich Sack<h4>Introduction</h4>PDL1 and its interaction with PD1 is implicated in immune dysfunction in TB and HIV. The expression of PDL1 on multiple subsets of monocytes as well as their associations with cytokines and microbial products have not been well studied.<h4>Method</h4>HIV (TB-HIV+), TB (TB+HIV-) and TB/HIV co-infected (TB+HIV+) patients as well as apparently healthy controls (TB-HIV-) were recruited. TB and HIV patients were treatment naïve while TB/HIV patients were both ART naïve and experienced but not yet started TB therapy. Monocyte subsets were evaluated for PDL1 expression by flow cytometry; plasma TNFα, IL6, IP10, IFNγ and IL10 were measured by Luminex; and cytokine mRNA from purified monocytes quantitated by qPCR. The association of PDL1 with cytokines, clinical and microbial indices, including HIV viral load, TB smear microscopy and TB urinary lipoarabinomannan (LAM) were assessed.<h4>Results</h4>Monocyte expression of PDL1 was significantly higher in TB, HIV and TB/HIV co-infected patients compared with healthy controls (p = 0.0001), with the highest levels in TB/HIV co-infected patients. The highest expression of PDL1 was on intermediate (CD14+CD16+) monocytes in all participant groups. PDL1 strongly correlated with HIV viral load in TB/HIV while weakly correlated in HIV. PDL1 levels moderately correlated with plasma TNFα, IL6, IP10, IFNγ and IL10 level in TB subjects whereas weakly correlated with TNFα and IP10 in HIV patients. However, cytokine mRNA from purified monocytes showed no association with either plasma cytokines or monocyte PDL1 expression, implying that if cytokines modulate PDL1, they are likely not originating from circulating monocytes themselves. These results underscore the importance of further characterization of multiple monocyte subsets and their phenotypic and functional differences in different disease states.https://doi.org/10.1371/journal.pone.0258122
spellingShingle Wegene Tamene
Meseret Abebe
Liya Wassie
Helina Mollalign
Katrin Bauer
Amha Kebede
Vincent C Marconi
Rawleigh Howe
Ulrich Sack
PDL1 expression on monocytes is associated with plasma cytokines in Tuberculosis and HIV.
PLoS ONE
title PDL1 expression on monocytes is associated with plasma cytokines in Tuberculosis and HIV.
title_full PDL1 expression on monocytes is associated with plasma cytokines in Tuberculosis and HIV.
title_fullStr PDL1 expression on monocytes is associated with plasma cytokines in Tuberculosis and HIV.
title_full_unstemmed PDL1 expression on monocytes is associated with plasma cytokines in Tuberculosis and HIV.
title_short PDL1 expression on monocytes is associated with plasma cytokines in Tuberculosis and HIV.
title_sort pdl1 expression on monocytes is associated with plasma cytokines in tuberculosis and hiv
url https://doi.org/10.1371/journal.pone.0258122
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