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cPLA2 regulates the expression of type I interferons and intracellular immunity to Chlamydia trachomatis.

Publication ,  Journal Article
Vignola, MJ; Kashatus, DF; Taylor, GA; Counter, CM; Valdivia, RH
Published in: J Biol Chem
July 9, 2010

Infection with the obligate bacterial intracellular pathogen Chlamydia trachomatis leads to the sustained activation of the small GTPase RAS and many of its downstream signaling components. In particular, the mitogen-activated protein kinase ERK and the calcium-dependent phospholipase cPLA(2) are activated and are important for the onset of inflammatory responses. In this study we tested if activation of ERK and cPLA(2) occurred as a result of RAS signaling during infection and determined the relative contribution of these signaling components to chlamydial replication and survival. We provide genetic and pharmacological evidence that during infection RAS, ERK, and, to a lesser extent, cPLA(2) activation are uncoupled, suggesting that Chlamydia activates individual components of this signaling pathway in a non-canonical manner. In human cell lines, inhibition of ERK or cPLA(2) signaling did not adversely impact C. trachomatis replication. In contrast, in murine cells, inhibition of ERK and cPLA(2) played a significant protective role against C. trachomatis. We determined that cPLA(2)-deficient murine cells are permissive for C. trachomatis replication because of their impaired expression of beta interferon and the induction of immunity-related GTPases (IRG) important for the containment of intracellular pathogens. Furthermore, the MAPK p38 was primarily responsible for cPLA(2) activation in Chlamydia-infected cells and IRG expression. Overall, these findings define a previously unrecognized role for cPLA(2) in the induction of cell autonomous cellular immunity to Chlamydia and highlight the many non-canonical signaling pathways engaged during infection.

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Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

July 9, 2010

Volume

285

Issue

28

Start / End Page

21625 / 21635

Location

United States

Related Subject Headings

  • ras Proteins
  • Phospholipases A2
  • Models, Biological
  • Microscopy, Fluorescence
  • Mice
  • Kinetics
  • Interferon Type I
  • Humans
  • Hela Cells
  • HeLa Cells
 

Citation

APA
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ICMJE
MLA
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Vignola, M. J., Kashatus, D. F., Taylor, G. A., Counter, C. M., & Valdivia, R. H. (2010). cPLA2 regulates the expression of type I interferons and intracellular immunity to Chlamydia trachomatis. J Biol Chem, 285(28), 21625–21635. https://doi.org/10.1074/jbc.M110.103010
Vignola, Mark J., David F. Kashatus, Gregory A. Taylor, Christopher M. Counter, and Raphael H. Valdivia. “cPLA2 regulates the expression of type I interferons and intracellular immunity to Chlamydia trachomatis.J Biol Chem 285, no. 28 (July 9, 2010): 21625–35. https://doi.org/10.1074/jbc.M110.103010.
Vignola MJ, Kashatus DF, Taylor GA, Counter CM, Valdivia RH. cPLA2 regulates the expression of type I interferons and intracellular immunity to Chlamydia trachomatis. J Biol Chem. 2010 Jul 9;285(28):21625–35.
Vignola, Mark J., et al. “cPLA2 regulates the expression of type I interferons and intracellular immunity to Chlamydia trachomatis.J Biol Chem, vol. 285, no. 28, July 2010, pp. 21625–35. Pubmed, doi:10.1074/jbc.M110.103010.
Vignola MJ, Kashatus DF, Taylor GA, Counter CM, Valdivia RH. cPLA2 regulates the expression of type I interferons and intracellular immunity to Chlamydia trachomatis. J Biol Chem. 2010 Jul 9;285(28):21625–21635.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

July 9, 2010

Volume

285

Issue

28

Start / End Page

21625 / 21635

Location

United States

Related Subject Headings

  • ras Proteins
  • Phospholipases A2
  • Models, Biological
  • Microscopy, Fluorescence
  • Mice
  • Kinetics
  • Interferon Type I
  • Humans
  • Hela Cells
  • HeLa Cells