Contribution of flagellin pattern recognition to intestinal inflammation during Salmonella enterica serotype typhimurium infection.
Salmonella enterica serotype Typhimurium causes acute inflammatory diarrhea in humans. Flagella contribute to intestinal inflammation, but the mechanism remains unclear since most mutations abrogating pattern recognition of flagellin also prevent motility and reduce bacterial invasion. To determine the contribution of flagellin pattern recognition to the generation of innate immune responses, we compared in two animal models a nonmotile, but flagellin-expressing and -secreting serotype Typhimurium strain (flgK mutant) to a nonmotile, non-flagellin-expressing strain (flgK fliC fljB mutant). In vitro, caspase-1 can be activated by cytosolic delivery of flagellin, resulting in release of the interferon gamma inducing factor interleukin-18 (IL-18). Experiments with streptomycin-pretreated caspase-1-deficient mice suggested that induction of gamma interferon expression in the murine cecum early (12 h) after serotype Typhimurium infection was caspase-1 dependent but independent of flagellin pattern recognition. In addition, mRNA levels of the CXC chemokines macrophage inflammatory protein 2 and keratinocyte-derived chemokine were markedly increased early after serotype Typhimurium infection of streptomycin-pretreated wild-type mice regardless of flagellin expression. In contrast, in bovine ligated ileal loops, flagellin pattern recognition contributed to increased mRNA levels of macrophage inflammatory protein 3alpha and more fluid accumulation at 2 h after infection. Collectively, our data suggest that pattern recognition of flagellin contributes to early innate host responses in the bovine ileal mucosa but not in the murine cecal mucosa.
Winter
Sebastian E
SE
Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Ave., Davis, CA 95616-8645, USA.
Thiennimitr
Parameth
P
Nuccio
Sean-Paul
SP
Haneda
Takeshi
T
Winter
Maria G
MG
Wilson
R Paul
RP
Russell
Joseph M
JM
Henry
Thomas
T
Tran
Quynh T
QT
Lawhon
Sara D
SD
Gomez
Gabriel
G
Bevins
Charles L
CL
Rüssmann
Holger
H
Monack
Denise M
DM
Adams
L Garry
LG
Bäumler
Andreas J
AJ
D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D002417:Cattle; D002432:Cecum / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005408:Flagellin / Q000235:genetics / Q000276:immunology*; D017353:Gene Deletion; D007082:Ileum / Q000276:immunology; D007249:Inflammation; D051379:Mice; D012480:Salmonella Infections / Q000276:immunology / Q000473:pathology*; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology*
D016207:Cytokines; D005408:Flagellin; D020170:Caspase 1