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PPARγ Ameliorates Mycobacterium tuberculosis H37Ra-Induced Foamy Macrophage Formation via the ABCG1-Dependent Cholesterol Efflux Pathway in THP-1 Macrophages

Foamy macrophages are present during the course of Mycobacterium tuberculosis (Mtb) infection and seems to be nutrient-rich reservoir and secure reservoir for the bacilli, which leads to bacterial persistence and infection transmission. Peroxisome proliferator activated receptor γ (PPARγ) is a key t...

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Autores principales: Ye, Yutao, Liu, Jun, Guo, Yang, Gao, Yujie, Rao, Jiayue, Su, Rigu, Zhang, Lu, Huang, Zikun, Luo, Qing, Li, Junming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008364/
https://www.ncbi.nlm.nih.gov/pubmed/35432274
http://dx.doi.org/10.3389/fmicb.2022.829870
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author Ye, Yutao
Liu, Jun
Guo, Yang
Gao, Yujie
Rao, Jiayue
Su, Rigu
Zhang, Lu
Huang, Zikun
Luo, Qing
Li, Junming
author_facet Ye, Yutao
Liu, Jun
Guo, Yang
Gao, Yujie
Rao, Jiayue
Su, Rigu
Zhang, Lu
Huang, Zikun
Luo, Qing
Li, Junming
author_sort Ye, Yutao
collection PubMed
description Foamy macrophages are present during the course of Mycobacterium tuberculosis (Mtb) infection and seems to be nutrient-rich reservoir and secure reservoir for the bacilli, which leads to bacterial persistence and infection transmission. Peroxisome proliferator activated receptor γ (PPARγ) is a key transcription factor for cholesterol metabolism in macrophages and its role in regulating atherosclerosis related foamy macrophages (FMs) formation has been well-studied. However, knowledge about the mechanism of PPARγ regulating Mtb infection induced FM formation remains very limited. In this study, we investigate the functional role of PPARγ in Mtb H37Ra infection-induced foamy macrophages formation. H37Ra infection induced a time-dependent decreased expression of PPARγ that paralleled the augmented lipid body formation in THP1-derived macrophages. PPARγ antagonist GW9662 significantly potentiate H37Ra induced lipid body formation and inhibit ABCG1 expression, overexpression of ABCG1 by transduced macrophages with lentivirus significantly reversed the promotion effect of GW9662 on FM formation. Moreover, Treatment with a TLR2 neutralizing antibody ameliorated the activation of ABCG1 by Mtb H37Ra without significantly effecting the suppression of PPARγ, suggesting a greater role for TLR2 to regulate ABCG1 compared to PPARγ. Overall, this study showed that PPARγ is involved in ameliorating FM formation by regulating ABCG1 expression, these observations expose a novel role of PPARγ in the Mtb infection induced FM formation.
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spelling pubmed-90083642022-04-15 PPARγ Ameliorates Mycobacterium tuberculosis H37Ra-Induced Foamy Macrophage Formation via the ABCG1-Dependent Cholesterol Efflux Pathway in THP-1 Macrophages Ye, Yutao Liu, Jun Guo, Yang Gao, Yujie Rao, Jiayue Su, Rigu Zhang, Lu Huang, Zikun Luo, Qing Li, Junming Front Microbiol Microbiology Foamy macrophages are present during the course of Mycobacterium tuberculosis (Mtb) infection and seems to be nutrient-rich reservoir and secure reservoir for the bacilli, which leads to bacterial persistence and infection transmission. Peroxisome proliferator activated receptor γ (PPARγ) is a key transcription factor for cholesterol metabolism in macrophages and its role in regulating atherosclerosis related foamy macrophages (FMs) formation has been well-studied. However, knowledge about the mechanism of PPARγ regulating Mtb infection induced FM formation remains very limited. In this study, we investigate the functional role of PPARγ in Mtb H37Ra infection-induced foamy macrophages formation. H37Ra infection induced a time-dependent decreased expression of PPARγ that paralleled the augmented lipid body formation in THP1-derived macrophages. PPARγ antagonist GW9662 significantly potentiate H37Ra induced lipid body formation and inhibit ABCG1 expression, overexpression of ABCG1 by transduced macrophages with lentivirus significantly reversed the promotion effect of GW9662 on FM formation. Moreover, Treatment with a TLR2 neutralizing antibody ameliorated the activation of ABCG1 by Mtb H37Ra without significantly effecting the suppression of PPARγ, suggesting a greater role for TLR2 to regulate ABCG1 compared to PPARγ. Overall, this study showed that PPARγ is involved in ameliorating FM formation by regulating ABCG1 expression, these observations expose a novel role of PPARγ in the Mtb infection induced FM formation. Frontiers Media S.A. 2022-03-31 /pmc/articles/PMC9008364/ /pubmed/35432274 http://dx.doi.org/10.3389/fmicb.2022.829870 Text en Copyright © 2022 Ye, Liu, Guo, Gao, Rao, Su, Zhang, Huang, Luo and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Ye, Yutao
Liu, Jun
Guo, Yang
Gao, Yujie
Rao, Jiayue
Su, Rigu
Zhang, Lu
Huang, Zikun
Luo, Qing
Li, Junming
PPARγ Ameliorates Mycobacterium tuberculosis H37Ra-Induced Foamy Macrophage Formation via the ABCG1-Dependent Cholesterol Efflux Pathway in THP-1 Macrophages
title PPARγ Ameliorates Mycobacterium tuberculosis H37Ra-Induced Foamy Macrophage Formation via the ABCG1-Dependent Cholesterol Efflux Pathway in THP-1 Macrophages
title_full PPARγ Ameliorates Mycobacterium tuberculosis H37Ra-Induced Foamy Macrophage Formation via the ABCG1-Dependent Cholesterol Efflux Pathway in THP-1 Macrophages
title_fullStr PPARγ Ameliorates Mycobacterium tuberculosis H37Ra-Induced Foamy Macrophage Formation via the ABCG1-Dependent Cholesterol Efflux Pathway in THP-1 Macrophages
title_full_unstemmed PPARγ Ameliorates Mycobacterium tuberculosis H37Ra-Induced Foamy Macrophage Formation via the ABCG1-Dependent Cholesterol Efflux Pathway in THP-1 Macrophages
title_short PPARγ Ameliorates Mycobacterium tuberculosis H37Ra-Induced Foamy Macrophage Formation via the ABCG1-Dependent Cholesterol Efflux Pathway in THP-1 Macrophages
title_sort pparγ ameliorates mycobacterium tuberculosis h37ra-induced foamy macrophage formation via the abcg1-dependent cholesterol efflux pathway in thp-1 macrophages
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008364/
https://www.ncbi.nlm.nih.gov/pubmed/35432274
http://dx.doi.org/10.3389/fmicb.2022.829870
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