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Tuberculosis (Edinb). 2018 Jul;111:170-177. doi: 10.1016/j.tube.2018.06.012. Epub 2018 Jun 21.

Deletion of PPARγ in lung macrophages provides an immunoprotective response against M. tuberculosis infection in mice.

Author information

1
Center for Microbial Interface Biology, Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA. Electronic address: evelynguirado@gmail.com.
2
Center for Microbial Interface Biology, Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA. Electronic address: murugesan.rajaram@osumc.edu.
3
Cardiovascular Research Institute, University of California, San Francisco, CA, USA. Electronic address: ajay.chawla@ucsf.edu.
4
Center for Microbial Interface Biology, Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA. Electronic address: joanna.daigle@usask.ca.
5
Comparative Pathology and Mouse Phenotyping Shared Resource, Department of Veterinary Biosciences, The Ohio State University, Arthur G. James Comprehensive Cancer Center, Columbus, OH, USA. Electronic address: laperle.1@osu.edu.
6
Center for Microbial Interface Biology, Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA. Electronic address: earnett@txbiomed.org.
7
Center for Microbial Interface Biology, Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA. Electronic address: joanneturner@txbiomed.org.
8
Center for Microbial Interface Biology, Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA. Electronic address: Lschlesinger@txbiomed.org.

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear transcription factor belonging to the superfamily of ligand-activated nuclear receptors. It is activated by diverse endogenous lipid metabolites as well as by exogenous ligands such as the thiazolidinediones. It regulates cellular metabolism, proliferation, differentiation, and inflammation, the latter in part through trans-repression of pro-inflammatory cytokines. PPARγ is highly expressed in alternatively activated alveolar macrophages (AMs), a primary host cell for airborne Mycobacterium tuberculosis (M.tb). Our previous in vitro study identified the importance of PPARγ activation through the mannose receptor (CD206) on human macrophages in enabling M. tb growth. The aim of the current study was to investigate the role of PPARγ in vivo during M. tb infection using a macrophage-specific PPARγ knock out mouse model with special emphasis on the lung environment. Our data show that the absence of PPARγ in lung macrophages reduces the growth of virulent M. tb, enhances pro-inflammatory cytokines and reduces granulomatous infiltration. These findings demonstrate that PPARγ activation, which down-regulates macrophage pro-inflammatory responses, impacts the lung's response to M. tb infection, thereby supporting PPARγ's role in tuberculosis (TB) pathogenesis.

KEYWORDS:

M. tuberculosis; Macrophage; PPARγ

PMID:
30029904
PMCID:
PMC6481684
DOI:
10.1016/j.tube.2018.06.012
[Indexed for MEDLINE]
Free PMC Article

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