Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes

Andrés Vazquez-Torres, Jessica Jones-Carson, Andreas J. Bäumler, Stanley Falkow, Raphael Valdivia, William Brown, Mysan Le, Ruth Berggren, W. Tony Parks and Ferric C. Fang ()
Additional contact information
Andrés Vazquez-Torres: Pathology, and Microbiology, University of Colorado Health Sciences Center
Jessica Jones-Carson: National Jewish Center for Immunology and Respiratory Medicine
Andreas J. Bäumler: Texas A&M University
Stanley Falkow: Stanford University School of Medicine
Raphael Valdivia: Stanford University School of Medicine
William Brown: Pathology, and Microbiology, University of Colorado Health Sciences Center
Mysan Le: Pathology, and Microbiology, University of Colorado Health Sciences Center
Ruth Berggren: Pathology, and Microbiology, University of Colorado Health Sciences Center
W. Tony Parks: Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health
Ferric C. Fang: Pathology, and Microbiology, University of Colorado Health Sciences Center

Nature, 1999, vol. 401, issue 6755, 804-808

Abstract: Abstract Specialized epithelia known as M cells overlying the lymphoid follicles of Peyer's patches are important in the mucosal immune system, but also provide a portal of entry for pathogens such as Salmonella typhimurium, Mycobacterium bovis, Shigella flexneri, Yersinia enterocolitica and reoviruses1,2,3,4. Penetration of intestinal M cells and epithelial cells by Salmonella typhimurium requires the invasion genes of Salmonella Pathogenicity Island 1 (SPI1)3,5,6,7,8,9. SPI1-deficient S. typhimurium strains gain access to the spleen following oral administration and cause lethal infection in mice5 without invading M cells3,9 or localizing in Peyer's patches10, which indicates that Salmonella uses an alternative strategy to disseminate from the gastrointestinal tract. Here we report that Salmonella is transported from the gastrointestinal tract to the bloodstream by CD18-expressing phagocytes, and that CD18-deficient mice are resistant to dissemination of Salmonella to the liver and spleen after oral administration. This CD18-dependent pathway of extraintestinal dissemination may be important for the development of systemic immunity to gastrointestinal pathogens, because oral challenge with SPI1-deficient S. typhimurium elicits a specific systemic IgG humoral immune response, despite an inability to stimulate production of specific mucosal IgA.

Date: 1999
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DOI: 10.1038/44593

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