The Pseudomonas aeruginosa Type III secretion system plays a dual role in the regulation of caspase-1 mediated IL-1beta maturation.
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.
Galle
M
M
Department of Molecular Biology, Ghent University, Ghent, Belgium.
Schotte
P
P
Haegman
M
M
Wullaert
A
A
Yang
H J
HJ
Jin
S
S
Beyaert
R
R
D036002:ADP Ribose Transferases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001427:Bacterial Toxins / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D053583:Interleukin-1beta / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D011552:Pseudomonas Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000378:metabolism*
D001427:Bacterial Toxins; D053583:Interleukin-1beta; D036002:ADP Ribose Transferases; C444820:exoenzyme S; D020170:Caspase 1