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

Tuberculosis
Evelyn GuiradoLarry S Schlesinger

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...Continue Reading

Citations

Feb 3, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shannon M LangeJoseph E Qualls
Mar 22, 2019·PLoS Pathogens·Chrissy M Leopold WagerLarry S Schlesinger
Nov 5, 2019·Frontiers in Immunology·Jayne Louise WilsonThomas Weichhart
Sep 29, 2020·Frontiers in Cellular and Infection Microbiology·Emer E Hackett, Frederick J Sheedy
Jan 27, 2019·Nature Reviews. Immunology·David G RussellBrian C VanderVen
Oct 7, 2020·Immunology·Frederick J Sheedy, Maziar Divangahi
Jan 21, 2021·International Journal of Molecular Sciences·Márcia V de CarvalhoAdriana R Silva
Mar 16, 2021·Frontiers in Cellular and Infection Microbiology·Dilara Kiran, Randall J Basaraba
Feb 28, 2021·Annual Review of Immunology·Mariëtta M Ravesloot-ChávezSarah A Stanley
Dec 22, 2020·Cytokine & Growth Factor Reviews·Marina DukhinovaAnna Shtro
Jul 25, 2021·International Journal of Molecular Sciences·Kazunari TanigawaKoichi Suzuki
Jul 18, 2021·Immunology and Cell Biology·Maxwell T StevensBernadette M Saunders
Aug 18, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Merilin Al Sharif
Nov 27, 2021·Expert Reviews in Molecular Medicine·Pamelia N LimAlissa C Rothchild

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