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IFNγ receptor down-regulation facilitates Legionella survival in alveolar macrophages.
- Source :
-
Journal of leukocyte biology [J Leukoc Biol] 2020 Feb; Vol. 107 (2), pp. 273-284. Date of Electronic Publication: 2019 Dec 02. - Publication Year :
- 2020
-
Abstract
- Legionella pneumophila is an opportunistic human pathogen and causative agent of the acute pneumonia known as Legionnaire's disease. Upon inhalation, the bacteria replicate in alveolar macrophages (AM), within an intracellular vacuole termed the Legionella-containing vacuole. We recently found that, in vivo, IFNγ was required for optimal clearance of intracellular L. pneumophila by monocyte-derived cells (MC), but the cytokine did not appear to influence clearance by AM. Here, we report that during L. pneumophila lung infection, expression of the IFNγ receptor subunit 1 (IFNGR1) is down-regulated in AM and neutrophils, but not MC, offering a possible explanation for why AM are unable to effectively restrict L. pneumophila replication in vivo. To test this, we used mice that constitutively express IFNGR1 in AM and found that prevention of IFNGR1 down-regulation enhanced the ability of AM to restrict L. pneumophila intracellular replication. IFNGR1 down-regulation was independent of the type IV Dot/Icm secretion system of L. pneumophila indicating that bacterial effector proteins were not involved. In contrast to previous work, we found that signaling via type I IFN receptors was not required for IFNGR1 down-regulation in macrophages but rather that MyD88- or Trif- mediated NF-κB activation was required. This work has uncovered an alternative signaling pathway responsible for IFNGR1 down-regulation in macrophages during bacterial infection.<br /> (©2019 Society for Leukocyte Biology.)
- Subjects :
- Animals
Down-Regulation
Interferon Type I metabolism
Legionella pneumophila metabolism
Legionnaires' Disease metabolism
Lung metabolism
Macrophages, Alveolar metabolism
Mice
Mice, Transgenic
Receptors, Interferon genetics
Receptors, Interferon metabolism
Signal Transduction
Interferon gamma Receptor
Legionella pneumophila growth & development
Legionnaires' Disease microbiology
Lung microbiology
Macrophages, Alveolar microbiology
NF-kappa B metabolism
Receptors, Interferon antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1938-3673
- Volume :
- 107
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of leukocyte biology
- Publication Type :
- Academic Journal
- Accession number :
- 31793076
- Full Text :
- https://doi.org/10.1002/JLB.4MA1019-152R