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Infection and Immunity, April 2005, p. 1978-1985, Vol. 73, No. 4
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.4.1978-1985.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Mast Cells Limit Systemic Bacterial Dissemination but Not Colitis in Response to Citrobacter rodentium

Olivia L. Wei, Ashley Hilliard, Daniel Kalman, and Melanie Sherman*

Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia

Received 30 June 2004/ Returned for modification 20 September 2004/ Accepted 8 November 2004

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.

* Corresponding author. Mailing address: Department of Pathology and Laboratory Medicine, Whitehead Research Bldg. 155, Emory University, 165 Michael St., Atlanta, GA 30322. Phone: (404) 712-1770. Fax: (404) 712-8538. E-mail: msherma{at}emory.edu.

Editor: A. D. O'Brien

Infection and Immunity, April 2005, p. 1978-1985, Vol. 73, No. 4
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.4.1978-1985.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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