Mast cells limit systemic bacterial dissemination but not colitis in response to Citrobacter rodentium.
Enteropathogenic Escherichia coli and enterohemorrhagic E. coli cause an inflammatory colitis in human patients characterized by neutrophil infiltration, proinflammatory cytokine expression, and crypt hyperplasia. Citrobacter rodentium causes a similar colitis in mice and serves as a model for enteropathogenic E. coli infection in humans. C. rodentium induces systemic T-cell-dependent antibody production that facilitates clearance of the bacteria and protects the host from reinfection. The role of innate immune cells in infectious colitis, however, is less well understood. In this study, we have determined the role of mast cells in the inflammatory response and disease induced by C. rodentium. Mice deficient in mast cells exhibit more severe colonic histopathology and have a higher mortality rate following infection with C. rodentium than do wild-type animals. Despite unimpaired neutrophil recruitment and lymphocyte activation, mast cell-deficient mice have a disseminated infection evident in crucial organ systems that contributes to sepsis. Importantly, mast cells also have the capacity to directly kill C. rodentium. Together, these results suggest that mast cells protect the host from systemic infection by reducing the bacterial load and preventing dissemination of the bacterium from the colon.
Wei
Olivia L
OL
Department of Pathology and Laboratory Medicine, Whitehead Research Bldg. 155, Emory University, 165 Michael St., Atlanta, GA 30322, USA.
Hilliard
Ashley
A
Kalman
Daniel
D
Sherman
Melanie
M
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000502:physiology; D044082:Citrobacter rodentium / Q000276:immunology / Q000472:pathogenicity*; D003092:Colitis / Q000276:immunology*; D003106:Colon / Q000382:microbiology*; D005260:Female; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis
D023181:Antimicrobial Cationic Peptides