Pathogen recognition receptor signaling accelerates phosphorylation-dependent degradation of IFNAR1

Juan Qian, Hui Zheng, Wei Chun HuangFu, Jianghuai Liu, Christopher J. Carbone, N. Adrian Leu, Darren P. Baker, Serge Y. Fuchs

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

An ability to sense pathogens by a number of specialized cell types including the dendritic cells plays a central role in host's defenses. Activation of these cells through the stimulation of the pathogen-recognition receptors induces the production of a number of cytokines including Type I interferons (IFNs) that mediate the diverse mechanisms of innate immunity. Type I IFNs interact with the Type I IFN receptor, composed of IFNAR1 and IFNAR2 chains, to mount the host defense responses. However, at the same time, Type I IFNs elicit potent anti-proliferative and pro-apoptotic effects that could be detrimental for IFN-producing cells. Here, we report that the activation of p38 kinase in response to pathogen-recognition receptors stimulation results in a series of phosphorylation events within the IFNAR1 chain of the Type I IFN receptor. This phosphorylation promotes IFNAR1 ubiquitination and acceleing and the protection of activated dendritic cells from the cytotoxic effects of autocrine or paracrine Type I IFN. In this paper we discuss a potential role of this mechanism in regulating the processes of innate immunity.

Original languageEnglish
Article numbere1002065
JournalPLoS Pathogens
Volume7
Issue number6
DOIs
Publication statusPublished - Jun 2011
Externally publishedYes

Fingerprint

Interferon Type I
Interferon alpha-beta Receptor
Phosphorylation
Innate Immunity
Dendritic Cells
Ubiquitination
Interferons
Phosphotransferases
Cell Count
Cytokines

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Pathogen recognition receptor signaling accelerates phosphorylation-dependent degradation of IFNAR1. / Qian, Juan; Zheng, Hui; HuangFu, Wei Chun; Liu, Jianghuai; Carbone, Christopher J.; Leu, N. Adrian; Baker, Darren P.; Fuchs, Serge Y.

In: PLoS Pathogens, Vol. 7, No. 6, e1002065, 06.2011.

Research output: Contribution to journalArticle

Qian, Juan ; Zheng, Hui ; HuangFu, Wei Chun ; Liu, Jianghuai ; Carbone, Christopher J. ; Leu, N. Adrian ; Baker, Darren P. ; Fuchs, Serge Y. / Pathogen recognition receptor signaling accelerates phosphorylation-dependent degradation of IFNAR1. In: PLoS Pathogens. 2011 ; Vol. 7, No. 6.
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