The Pseudomonas aeruginosa Type III secretion system plays a dual role in the regulation of caspase-1 mediated IL-1beta maturation

J Cell Mol Med. Sep-Oct 2008;12(5A):1767-76. doi: 10.1111/j.1582-4934.2007.00190.x. Epub 2007 Dec 10.

Abstract

Pseudomonas aeruginosa is an opportunistic bacterial pathogen that forms a serious problem for immunocompromised patients and also the leading cause of mortality in cystic fibrosis. The overall importance of a functional Type III secretion system (T3SS) in P. aeruginosa virulence has been well established, but the underlying mechanisms are still unclear. Using in vitro infected macrophages as w as a murine model of acute lung infection, we show that the Caspase-1 mediated maturation and secretion of IL-1beta needs a translocation competent T3SS and Flagellin, but not the Type III effector proteins ExoS, ExoT and ExoY. However, ExoS was found to negative regulate the P. aeruginosa induced IL-1beta maturation by a mechanism that is dependent on its ADP ribosyltransferase activity. Moreov ExoS deficiency also switched the mode of macrophage death from apoptosis to pro-inflammatory pyroptosis. Altogether, these data demonstrate a dual role for the P. aeruginosa T3SS in the regulation of Caspase-1 mediated IL-1beta production and provide new insights into the mechanisms of immune evasion by this pathogen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP Ribose Transferases / metabolism
  • Animals
  • Apoptosis
  • Bacterial Toxins / metabolism
  • Caspase 1 / metabolism*
  • Cells, Cultured
  • Female
  • Interleukin-1beta / metabolism*
  • Macrophages / cytology
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred DBA
  • Pseudomonas Infections / genetics
  • Pseudomonas Infections / metabolism
  • Pseudomonas Infections / pathology
  • Pseudomonas aeruginosa / metabolism*

Substances

  • Bacterial Toxins
  • Interleukin-1beta
  • ADP Ribose Transferases
  • exoenzyme S
  • Caspase 1