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.
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Acknowledgements
This work was supported in part by grants from the NIH (A.V.T., J.J.C., A.B., R.B. and F.F.), the United States Department of Agriculture (A.B.), and the James Biundo Foundation (F.F.). The authors are grateful to E. Balish for constructive review of the manuscript and thank F. Heffron and S. Moller for the gifts of strains CL1509 and SM022, respectively.
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Vazquez-Torres, A., Jones-Carson, J., Bäumler, A. et al. Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes. Nature 401, 804–808 (1999). https://doi.org/10.1038/44593
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DOI: https://doi.org/10.1038/44593
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