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Lack of PPARγ in Myeloid Cells Confers Resistance to Listeria monocytogenes Infection
The peroxisomal proliferator-activated receptor γ (PPARγ) is a nuclear receptor that controls inflammation and immunity. Innate immune defense against bacterial infection appears to be compromised by PPARγ. The relevance of PPARγ in myeloid cells, that organize anti-bacterial immunity, for the outco...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3357414/ https://www.ncbi.nlm.nih.gov/pubmed/22629382 http://dx.doi.org/10.1371/journal.pone.0037349 |
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author | Abdullah, Zeinab Geiger, Sergej Nino-Castro, Andrea Böttcher, Jan P. Muraliv, Eugenia Gaidt, Moritz Schildberg, Frank A. Riethausen, Kati Flossdorf, Juliane Krebs, Wolfgang Chakraborty, Trinad Kurts, Christian Schultze, Joachim L. Knolle, Percy A. Klotz, Luisa |
author_facet | Abdullah, Zeinab Geiger, Sergej Nino-Castro, Andrea Böttcher, Jan P. Muraliv, Eugenia Gaidt, Moritz Schildberg, Frank A. Riethausen, Kati Flossdorf, Juliane Krebs, Wolfgang Chakraborty, Trinad Kurts, Christian Schultze, Joachim L. Knolle, Percy A. Klotz, Luisa |
author_sort | Abdullah, Zeinab |
collection | PubMed |
description | The peroxisomal proliferator-activated receptor γ (PPARγ) is a nuclear receptor that controls inflammation and immunity. Innate immune defense against bacterial infection appears to be compromised by PPARγ. The relevance of PPARγ in myeloid cells, that organize anti-bacterial immunity, for the outcome of immune responses against intracellular bacteria such as Listeria monocytogenes in vivo is unknown. We found that Listeria monocytogenes infection of macrophages rapidly led to increased expression of PPARγ. This prompted us to investigate whether PPARγ in myeloid cells influences innate immunity against Listeria monocytogenes infection by using transgenic mice with myeloid-cell specific ablation of PPARγ (LysMCre×PPARγ(flox/flox)). Loss of PPARγ in myeloid cells results in enhanced innate immune defense against Listeria monocytogenes infection both, in vitro and in vivo. This increased resistance against infection was characterized by augmented levels of bactericidal factors and inflammatory cytokines: ROS, NO, IFNγ TNF IL-6 and IL-12. Moreover, myeloid cell-specific loss of PPARγ enhanced chemokine and adhesion molecule expression leading to improved recruitment of inflammatory Ly6C(hi) monocytes to sites of infection. Importantly, increased resistance against Listeria infection in the absence of PPARγ was not accompanied by enhanced immunopathology. Our results elucidate a yet unknown regulatory network in myeloid cells that is governed by PPARγ and restrains both listeriocidal activity and recruitment of inflammatory monocytes during Listeria infection, which may contribute to bacterial immune escape. Pharmacological interference with PPARγ activity in myeloid cells might represent a novel strategy to overcome intracellular bacterial infection. |
format | Online Article Text |
id | pubmed-3357414 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33574142012-05-24 Lack of PPARγ in Myeloid Cells Confers Resistance to Listeria monocytogenes Infection Abdullah, Zeinab Geiger, Sergej Nino-Castro, Andrea Böttcher, Jan P. Muraliv, Eugenia Gaidt, Moritz Schildberg, Frank A. Riethausen, Kati Flossdorf, Juliane Krebs, Wolfgang Chakraborty, Trinad Kurts, Christian Schultze, Joachim L. Knolle, Percy A. Klotz, Luisa PLoS One Research Article The peroxisomal proliferator-activated receptor γ (PPARγ) is a nuclear receptor that controls inflammation and immunity. Innate immune defense against bacterial infection appears to be compromised by PPARγ. The relevance of PPARγ in myeloid cells, that organize anti-bacterial immunity, for the outcome of immune responses against intracellular bacteria such as Listeria monocytogenes in vivo is unknown. We found that Listeria monocytogenes infection of macrophages rapidly led to increased expression of PPARγ. This prompted us to investigate whether PPARγ in myeloid cells influences innate immunity against Listeria monocytogenes infection by using transgenic mice with myeloid-cell specific ablation of PPARγ (LysMCre×PPARγ(flox/flox)). Loss of PPARγ in myeloid cells results in enhanced innate immune defense against Listeria monocytogenes infection both, in vitro and in vivo. This increased resistance against infection was characterized by augmented levels of bactericidal factors and inflammatory cytokines: ROS, NO, IFNγ TNF IL-6 and IL-12. Moreover, myeloid cell-specific loss of PPARγ enhanced chemokine and adhesion molecule expression leading to improved recruitment of inflammatory Ly6C(hi) monocytes to sites of infection. Importantly, increased resistance against Listeria infection in the absence of PPARγ was not accompanied by enhanced immunopathology. Our results elucidate a yet unknown regulatory network in myeloid cells that is governed by PPARγ and restrains both listeriocidal activity and recruitment of inflammatory monocytes during Listeria infection, which may contribute to bacterial immune escape. Pharmacological interference with PPARγ activity in myeloid cells might represent a novel strategy to overcome intracellular bacterial infection. Public Library of Science 2012-05-21 /pmc/articles/PMC3357414/ /pubmed/22629382 http://dx.doi.org/10.1371/journal.pone.0037349 Text en Abdullah et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Abdullah, Zeinab Geiger, Sergej Nino-Castro, Andrea Böttcher, Jan P. Muraliv, Eugenia Gaidt, Moritz Schildberg, Frank A. Riethausen, Kati Flossdorf, Juliane Krebs, Wolfgang Chakraborty, Trinad Kurts, Christian Schultze, Joachim L. Knolle, Percy A. Klotz, Luisa Lack of PPARγ in Myeloid Cells Confers Resistance to Listeria monocytogenes Infection |
title | Lack of PPARγ in Myeloid Cells Confers Resistance to Listeria monocytogenes Infection |
title_full | Lack of PPARγ in Myeloid Cells Confers Resistance to Listeria monocytogenes Infection |
title_fullStr | Lack of PPARγ in Myeloid Cells Confers Resistance to Listeria monocytogenes Infection |
title_full_unstemmed | Lack of PPARγ in Myeloid Cells Confers Resistance to Listeria monocytogenes Infection |
title_short | Lack of PPARγ in Myeloid Cells Confers Resistance to Listeria monocytogenes Infection |
title_sort | lack of pparγ in myeloid cells confers resistance to listeria monocytogenes infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3357414/ https://www.ncbi.nlm.nih.gov/pubmed/22629382 http://dx.doi.org/10.1371/journal.pone.0037349 |
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