Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes

Andrés Vazquez-Terres, Jessica Jones-Carson, Andreas J. Bäumler, Stanley Falkow, Raphael Valdivia, William Brown, Mysan Lo, Ruth Berggren, W. Tony Parks, Ferric C. Fang*

*Corresponding author for this work

Research output: Contribution to journalArticle

484 Scopus citations

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 reoviruses. Penetration of intestinal M cells and epithelial cells by Salmonella typhimurium requires the invasion genes of Salmonella Pathogenicity Island 1 (SPI1). SPI1-deficient S. typhimurium strains gain access to the spleen following oral administration and cause lethal infection in mice without invading M cells or localizing in Peyer's patches, 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.

Original languageEnglish (US)
Pages (from-to)804-808
Number of pages5
JournalNature
Volume401
Issue number6755
DOIs
StatePublished - Oct 21 1999

ASJC Scopus subject areas

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    Vazquez-Terres, A., Jones-Carson, J., Bäumler, A. J., Falkow, S., Valdivia, R., Brown, W., Lo, M., Berggren, R., Parks, W. T., & Fang, F. C. (1999). Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes. Nature, 401(6755), 804-808. https://doi.org/10.1038/44593