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A20 (Tnfaip3) deficiency in myeloid cells protects against influenza A virus infection

Jonathan Maelfait UGent, Kenny Roose UGent, Pieter Bogaert UGent, Mozes Sze UGent, Xavier Saelens UGent, Manolis Pasparakis, Isabelle Carpentier UGent, Geert van Loo UGent and Rudi Beyaert UGent (2012) PLOS PATHOGENS. 8(3).
abstract
The innate immune response provides the first line of defense against viruses and other pathogens by responding to specific microbial molecules. Influenza A virus (IAV) produces double-stranded RNA as an intermediate during the replication life cycle, which activates the intracellular pathogen recognition receptor RIG-I and induces the production of proinflammatory cytokines and antiviral interferon. Understanding the mechanisms that regulate innate immune responses to IAV and other viruses is of key importance to develop novel therapeutic strategies. Here we used myeloid cell specific A20 knockout mice to examine the role of the ubiquitin-editing protein A20 in the response of myeloid cells to IAV infection. A20 deficient macrophages were hyperresponsive to double stranded RNA and IAV infection, as illustrated by enhanced NF-kappa B and IRF3 activation, concomitant with increased production of proinflammatory cytokines, chemokines and type I interferon. In vivo this was associated with an increased number of alveolar macrophages and neutrophils in the lungs of IAV infected mice. Surprisingly, myeloid cell specific A20 knockout mice are protected against lethal IAV infection. These results challenge the general belief that an excessive host proinflammatory response is associated with IAV-induced lethality, and suggest that under certain conditions inhibition of A20 might be of interest in the management of IAV infections.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
PATTERN-RECOGNITION RECEPTORS, INNATE IMMUNE-RESPONSES, INDUCIBLE GENE-I, NF-KAPPA-B, KINASE-RELATED KINASES, TUMOR-SUPPRESSOR CYLD, E3 UBIQUITIN LIGASE, CD8(+) T-CELLS, RIG-I, ALVEOLAR MACROPHAGES
journal title
PLOS PATHOGENS
PLoS Pathog.
volume
8
issue
3
article_number
e1002570
pages
11 pages
Web of Science type
Article
Web of Science id
000302225600024
ISSN
1553-7366
DOI
10.1371/journal.ppat.1002570
project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
language
English
UGent publication?
yes
classification
A1
copyright statement
I have retained and own the full copyright for this publication
id
2095247
handle
http://hdl.handle.net/1854/LU-2095247
date created
2012-04-26 15:21:18
date last changed
2014-05-12 10:59:41
@article{2095247,
  abstract     = {The innate immune response provides the first line of defense against viruses and other pathogens by responding to specific microbial molecules. Influenza A virus (IAV) produces double-stranded RNA as an intermediate during the replication life cycle, which activates the intracellular pathogen recognition receptor RIG-I and induces the production of proinflammatory cytokines and antiviral interferon. Understanding the mechanisms that regulate innate immune responses to IAV and other viruses is of key importance to develop novel therapeutic strategies. Here we used myeloid cell specific A20 knockout mice to examine the role of the ubiquitin-editing protein A20 in the response of myeloid cells to IAV infection. A20 deficient macrophages were hyperresponsive to double stranded RNA and IAV infection, as illustrated by enhanced NF-kappa B and IRF3 activation, concomitant with increased production of proinflammatory cytokines, chemokines and type I interferon. In vivo this was associated with an increased number of alveolar macrophages and neutrophils in the lungs of IAV infected mice. Surprisingly, myeloid cell specific A20 knockout mice are protected against lethal IAV infection. These results challenge the general belief that an excessive host proinflammatory response is associated with IAV-induced lethality, and suggest that under certain conditions inhibition of A20 might be of interest in the management of IAV infections.},
  articleno    = {e1002570},
  author       = {Maelfait, Jonathan and Roose, Kenny and Bogaert, Pieter and Sze, Mozes and Saelens, Xavier and Pasparakis, Manolis and Carpentier, Isabelle and van Loo, Geert and Beyaert, Rudi},
  issn         = {1553-7366},
  journal      = {PLOS PATHOGENS},
  keyword      = {PATTERN-RECOGNITION RECEPTORS,INNATE IMMUNE-RESPONSES,INDUCIBLE GENE-I,NF-KAPPA-B,KINASE-RELATED KINASES,TUMOR-SUPPRESSOR CYLD,E3 UBIQUITIN LIGASE,CD8(+) T-CELLS,RIG-I,ALVEOLAR MACROPHAGES},
  language     = {eng},
  number       = {3},
  pages        = {11},
  title        = {A20 (Tnfaip3) deficiency in myeloid cells protects against influenza A virus infection},
  url          = {http://dx.doi.org/10.1371/journal.ppat.1002570},
  volume       = {8},
  year         = {2012},
}

Chicago
Maelfait, Jonathan, Kenny Roose, Pieter Bogaert, Mozes Sze, Xavier Saelens, Manolis Pasparakis, Isabelle Carpentier, Geert van Loo, and Rudi Beyaert. 2012. “A20 (Tnfaip3) Deficiency in Myeloid Cells Protects Against Influenza A Virus Infection.” Plos Pathogens 8 (3).
APA
Maelfait, J., Roose, K., Bogaert, P., Sze, M., Saelens, X., Pasparakis, M., Carpentier, I., et al. (2012). A20 (Tnfaip3) deficiency in myeloid cells protects against influenza A virus infection. PLOS PATHOGENS, 8(3).
Vancouver
1.
Maelfait J, Roose K, Bogaert P, Sze M, Saelens X, Pasparakis M, et al. A20 (Tnfaip3) deficiency in myeloid cells protects against influenza A virus infection. PLOS PATHOGENS. 2012;8(3).
MLA
Maelfait, Jonathan, Kenny Roose, Pieter Bogaert, et al. “A20 (Tnfaip3) Deficiency in Myeloid Cells Protects Against Influenza A Virus Infection.” PLOS PATHOGENS 8.3 (2012): n. pag. Print.