Absence of poly(ADP-ribose) polymerase 1 delays the onset of Salmonella enterica serovar Typhimurium-induced gut inflammation.
The immune system comprises an innate and an adaptive immune response to combat pathogenic agents. The human enteropathogen Salmonella enterica serovar Typhimurium invades the intestinal mucosa and triggers an early innate proinflammatory host gene response, which results in diarrheal disease. Several host factors, including transcription factors and transcription coregulators, are involved in the acute early response to Salmonella infection. We found in a mouse model of enterocolitis induced by S. Typhimurium that the absence of the nuclear protein poly(ADP-ribose) polymerase 1 (PARP1), a previously described cofactor for NF-kappaB-mediated proinflammatory gene expression, is associated with a delayed proinflammatory immune response after Salmonella infection. Our data reveal that PARP1 is expressed in the proliferative zone of cecum crypts, where it is required for the efficient expression of proinflammatory genes, many of which are related to interferon signaling. Consequently, animals lacking PARP1 show impaired infiltration of immune cells into the gut, with severely delayed inflammation.
Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Matthias
M
Altmeyer
Manja
M
Barthel
Matthias
M
Eberhard
Hubert
H
Rehrauer
Wolf-Dietrich
WD
Hardt
Michael O
MO
Hottiger
D000818:Animals; D002432:Cecum / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008853:Microscopy; D008856:Microscopy, Fluorescence; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000172:deficiency / Q000276:immunology*; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000473:pathology*; D012486:Salmonella typhimurium / Q000276:immunology* / Q000472:pathogenicity*
C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases