CD14+ macrophages that accumulate in the colon of African AIDS patients express pro-inflammatory cytokines and are responsive to lipopolysaccharide

Edana Cassol, Theresa Rossouw, Susan Malfeld, Phetole Mahasha, Tomas Slavik, Chris Seebregts, Robert Bond, Johannie du Plessis, Carl Janssen, Tania Roskams, Frederik Nevens, Massimo Alfano, Guido Poli, Schalk W. van der Merwe

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: Intestinal macrophages are key regulators of inflammatory responses to the gut microbiome and play a central role in maintaining tissue homeostasis and epithelial integrity. However, little is known about the role of these cells in HIV infection, a disease fuelled by intestinal inflammation, a loss of epithelial barrier function and increased microbial translocation (MT). Methods: Phenotypic and functional characterization of intestinal macrophages was performed for 23 African AIDS patients with chronic diarrhea and/or weight loss and 11 HIV-negative Africans with and without inflammatory bowel disease (IBD). AIDS patients were treated with cotrimoxazole for the prevention of opportunistic infections (OIs). Macrophage phenotype was assessed by flow cytometry and immuno-histochemistry (IHC); production of proinflammatory mediators by IHC and Qiagen PCR Arrays; in vitro secretion of cytokines by the Bio-Plex Suspension Array System. Statistical analyses were performed using Spearman's correlation and Wilcoxon matched-pair tests. Results between groups were analyzed using the Kruskal-Wallis with Dunn's post-test and the Mann-Whitney U tests. Results: None of the study participants had evidence of enteric co-infections as assessed by stool analysis and histology. Compared to healthy HIV-negative controls, the colon of AIDS patients was highly inflamed with increased infiltration of inflammatory cells and increased mRNA expression of proinflammatory cytokine (tumour necrosis factor (TNF)-aα, interleukin (IL)-1β, IFN-γ, and IL-18), chemokines (chemokine (C-C motif) ligand (CCL)2 and chemokine (C-X-C) motif ligand (CXCL)10) and transcription factors (TNF receptor-associated factor (TRAF)6 and T-box (TXB)21). IHC revealed significant co-localization of TNF-aα and IL-1β with CD68+ cells. As in IBD, HIV was associated with a marked increase in macrophages expressing innate response receptors including CD14, the co-receptor for lipopolysaccharide (LPS). The frequency of CD14+ macrophages correlated positively with plasma LPS, a marker of MT. Total unfractionated mucosal mononuclear cells (MMC) isolated from the colon of AIDS patients, but not MMC depleted of CD14+ cells, secreted increased levels of proinflammatory cytokines ex vivo in response to LPS. Conclusions: Intestinal macrophages, in the absence of overt OIs, play an important role in driving persistent inflammation in HIV patients with late-stage disease and diarrhea. These results suggest intensified treatment strategies that target inflammatory processes in intestinal macrophages may be highly beneficial in restoring the epithelial barrier and limiting MT in HIV-infected patients.

Original languageEnglish
JournalBMC Infectious Diseases
Volume15
Issue number1
DOIs
Publication statusPublished - Oct 17 2015

Fingerprint

Lipopolysaccharides
Colon
Acquired Immunodeficiency Syndrome
Macrophages
Cytokines
HIV
Opportunistic Infections
Interleukin-1
Inflammatory Bowel Diseases
Diarrhea
Tumor Necrosis Factor-alpha
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
CD14 Antigens
Chemokine CXCL10
Inflammation
Intestinal Diseases
Interleukin-18
Chemokine CCL2
Sulfamethoxazole Drug Combination Trimethoprim
Nonparametric Statistics

Keywords

  • AIDS
  • Colon
  • Immune activation
  • Inflammation
  • Macrophages

ASJC Scopus subject areas

  • Infectious Diseases

Cite this

CD14+ macrophages that accumulate in the colon of African AIDS patients express pro-inflammatory cytokines and are responsive to lipopolysaccharide. / Cassol, Edana; Rossouw, Theresa; Malfeld, Susan; Mahasha, Phetole; Slavik, Tomas; Seebregts, Chris; Bond, Robert; du Plessis, Johannie; Janssen, Carl; Roskams, Tania; Nevens, Frederik; Alfano, Massimo; Poli, Guido; van der Merwe, Schalk W.

In: BMC Infectious Diseases, Vol. 15, No. 1, 17.10.2015.

Research output: Contribution to journalArticle

Cassol, E, Rossouw, T, Malfeld, S, Mahasha, P, Slavik, T, Seebregts, C, Bond, R, du Plessis, J, Janssen, C, Roskams, T, Nevens, F, Alfano, M, Poli, G & van der Merwe, SW 2015, 'CD14+ macrophages that accumulate in the colon of African AIDS patients express pro-inflammatory cytokines and are responsive to lipopolysaccharide', BMC Infectious Diseases, vol. 15, no. 1. https://doi.org/10.1186/s12879-015-1176-5
Cassol, Edana ; Rossouw, Theresa ; Malfeld, Susan ; Mahasha, Phetole ; Slavik, Tomas ; Seebregts, Chris ; Bond, Robert ; du Plessis, Johannie ; Janssen, Carl ; Roskams, Tania ; Nevens, Frederik ; Alfano, Massimo ; Poli, Guido ; van der Merwe, Schalk W. / CD14+ macrophages that accumulate in the colon of African AIDS patients express pro-inflammatory cytokines and are responsive to lipopolysaccharide. In: BMC Infectious Diseases. 2015 ; Vol. 15, No. 1.
@article{2dd303b24ab54cc99d8ae3b7cd967977,
title = "CD14+ macrophages that accumulate in the colon of African AIDS patients express pro-inflammatory cytokines and are responsive to lipopolysaccharide",
abstract = "Background: Intestinal macrophages are key regulators of inflammatory responses to the gut microbiome and play a central role in maintaining tissue homeostasis and epithelial integrity. However, little is known about the role of these cells in HIV infection, a disease fuelled by intestinal inflammation, a loss of epithelial barrier function and increased microbial translocation (MT). Methods: Phenotypic and functional characterization of intestinal macrophages was performed for 23 African AIDS patients with chronic diarrhea and/or weight loss and 11 HIV-negative Africans with and without inflammatory bowel disease (IBD). AIDS patients were treated with cotrimoxazole for the prevention of opportunistic infections (OIs). Macrophage phenotype was assessed by flow cytometry and immuno-histochemistry (IHC); production of proinflammatory mediators by IHC and Qiagen PCR Arrays; in vitro secretion of cytokines by the Bio-Plex Suspension Array System. Statistical analyses were performed using Spearman's correlation and Wilcoxon matched-pair tests. Results between groups were analyzed using the Kruskal-Wallis with Dunn's post-test and the Mann-Whitney U tests. Results: None of the study participants had evidence of enteric co-infections as assessed by stool analysis and histology. Compared to healthy HIV-negative controls, the colon of AIDS patients was highly inflamed with increased infiltration of inflammatory cells and increased mRNA expression of proinflammatory cytokine (tumour necrosis factor (TNF)-aα, interleukin (IL)-1β, IFN-γ, and IL-18), chemokines (chemokine (C-C motif) ligand (CCL)2 and chemokine (C-X-C) motif ligand (CXCL)10) and transcription factors (TNF receptor-associated factor (TRAF)6 and T-box (TXB)21). IHC revealed significant co-localization of TNF-aα and IL-1β with CD68+ cells. As in IBD, HIV was associated with a marked increase in macrophages expressing innate response receptors including CD14, the co-receptor for lipopolysaccharide (LPS). The frequency of CD14+ macrophages correlated positively with plasma LPS, a marker of MT. Total unfractionated mucosal mononuclear cells (MMC) isolated from the colon of AIDS patients, but not MMC depleted of CD14+ cells, secreted increased levels of proinflammatory cytokines ex vivo in response to LPS. Conclusions: Intestinal macrophages, in the absence of overt OIs, play an important role in driving persistent inflammation in HIV patients with late-stage disease and diarrhea. These results suggest intensified treatment strategies that target inflammatory processes in intestinal macrophages may be highly beneficial in restoring the epithelial barrier and limiting MT in HIV-infected patients.",
keywords = "AIDS, Colon, Immune activation, Inflammation, Macrophages",
author = "Edana Cassol and Theresa Rossouw and Susan Malfeld and Phetole Mahasha and Tomas Slavik and Chris Seebregts and Robert Bond and {du Plessis}, Johannie and Carl Janssen and Tania Roskams and Frederik Nevens and Massimo Alfano and Guido Poli and {van der Merwe}, {Schalk W.}",
year = "2015",
month = "10",
day = "17",
doi = "10.1186/s12879-015-1176-5",
language = "English",
volume = "15",
journal = "BMC Infectious Diseases",
issn = "1471-2334",
publisher = "BioMed Central Ltd.",
number = "1",

}

TY - JOUR

T1 - CD14+ macrophages that accumulate in the colon of African AIDS patients express pro-inflammatory cytokines and are responsive to lipopolysaccharide

AU - Cassol, Edana

AU - Rossouw, Theresa

AU - Malfeld, Susan

AU - Mahasha, Phetole

AU - Slavik, Tomas

AU - Seebregts, Chris

AU - Bond, Robert

AU - du Plessis, Johannie

AU - Janssen, Carl

AU - Roskams, Tania

AU - Nevens, Frederik

AU - Alfano, Massimo

AU - Poli, Guido

AU - van der Merwe, Schalk W.

PY - 2015/10/17

Y1 - 2015/10/17

N2 - Background: Intestinal macrophages are key regulators of inflammatory responses to the gut microbiome and play a central role in maintaining tissue homeostasis and epithelial integrity. However, little is known about the role of these cells in HIV infection, a disease fuelled by intestinal inflammation, a loss of epithelial barrier function and increased microbial translocation (MT). Methods: Phenotypic and functional characterization of intestinal macrophages was performed for 23 African AIDS patients with chronic diarrhea and/or weight loss and 11 HIV-negative Africans with and without inflammatory bowel disease (IBD). AIDS patients were treated with cotrimoxazole for the prevention of opportunistic infections (OIs). Macrophage phenotype was assessed by flow cytometry and immuno-histochemistry (IHC); production of proinflammatory mediators by IHC and Qiagen PCR Arrays; in vitro secretion of cytokines by the Bio-Plex Suspension Array System. Statistical analyses were performed using Spearman's correlation and Wilcoxon matched-pair tests. Results between groups were analyzed using the Kruskal-Wallis with Dunn's post-test and the Mann-Whitney U tests. Results: None of the study participants had evidence of enteric co-infections as assessed by stool analysis and histology. Compared to healthy HIV-negative controls, the colon of AIDS patients was highly inflamed with increased infiltration of inflammatory cells and increased mRNA expression of proinflammatory cytokine (tumour necrosis factor (TNF)-aα, interleukin (IL)-1β, IFN-γ, and IL-18), chemokines (chemokine (C-C motif) ligand (CCL)2 and chemokine (C-X-C) motif ligand (CXCL)10) and transcription factors (TNF receptor-associated factor (TRAF)6 and T-box (TXB)21). IHC revealed significant co-localization of TNF-aα and IL-1β with CD68+ cells. As in IBD, HIV was associated with a marked increase in macrophages expressing innate response receptors including CD14, the co-receptor for lipopolysaccharide (LPS). The frequency of CD14+ macrophages correlated positively with plasma LPS, a marker of MT. Total unfractionated mucosal mononuclear cells (MMC) isolated from the colon of AIDS patients, but not MMC depleted of CD14+ cells, secreted increased levels of proinflammatory cytokines ex vivo in response to LPS. Conclusions: Intestinal macrophages, in the absence of overt OIs, play an important role in driving persistent inflammation in HIV patients with late-stage disease and diarrhea. These results suggest intensified treatment strategies that target inflammatory processes in intestinal macrophages may be highly beneficial in restoring the epithelial barrier and limiting MT in HIV-infected patients.

AB - Background: Intestinal macrophages are key regulators of inflammatory responses to the gut microbiome and play a central role in maintaining tissue homeostasis and epithelial integrity. However, little is known about the role of these cells in HIV infection, a disease fuelled by intestinal inflammation, a loss of epithelial barrier function and increased microbial translocation (MT). Methods: Phenotypic and functional characterization of intestinal macrophages was performed for 23 African AIDS patients with chronic diarrhea and/or weight loss and 11 HIV-negative Africans with and without inflammatory bowel disease (IBD). AIDS patients were treated with cotrimoxazole for the prevention of opportunistic infections (OIs). Macrophage phenotype was assessed by flow cytometry and immuno-histochemistry (IHC); production of proinflammatory mediators by IHC and Qiagen PCR Arrays; in vitro secretion of cytokines by the Bio-Plex Suspension Array System. Statistical analyses were performed using Spearman's correlation and Wilcoxon matched-pair tests. Results between groups were analyzed using the Kruskal-Wallis with Dunn's post-test and the Mann-Whitney U tests. Results: None of the study participants had evidence of enteric co-infections as assessed by stool analysis and histology. Compared to healthy HIV-negative controls, the colon of AIDS patients was highly inflamed with increased infiltration of inflammatory cells and increased mRNA expression of proinflammatory cytokine (tumour necrosis factor (TNF)-aα, interleukin (IL)-1β, IFN-γ, and IL-18), chemokines (chemokine (C-C motif) ligand (CCL)2 and chemokine (C-X-C) motif ligand (CXCL)10) and transcription factors (TNF receptor-associated factor (TRAF)6 and T-box (TXB)21). IHC revealed significant co-localization of TNF-aα and IL-1β with CD68+ cells. As in IBD, HIV was associated with a marked increase in macrophages expressing innate response receptors including CD14, the co-receptor for lipopolysaccharide (LPS). The frequency of CD14+ macrophages correlated positively with plasma LPS, a marker of MT. Total unfractionated mucosal mononuclear cells (MMC) isolated from the colon of AIDS patients, but not MMC depleted of CD14+ cells, secreted increased levels of proinflammatory cytokines ex vivo in response to LPS. Conclusions: Intestinal macrophages, in the absence of overt OIs, play an important role in driving persistent inflammation in HIV patients with late-stage disease and diarrhea. These results suggest intensified treatment strategies that target inflammatory processes in intestinal macrophages may be highly beneficial in restoring the epithelial barrier and limiting MT in HIV-infected patients.

KW - AIDS

KW - Colon

KW - Immune activation

KW - Inflammation

KW - Macrophages

UR - http://www.scopus.com/inward/record.url?scp=84945205256&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84945205256&partnerID=8YFLogxK

U2 - 10.1186/s12879-015-1176-5

DO - 10.1186/s12879-015-1176-5

M3 - Article

VL - 15

JO - BMC Infectious Diseases

JF - BMC Infectious Diseases

SN - 1471-2334

IS - 1

ER -