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Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes

Nature volume 401, pages 804–808 (1999)Cite this article

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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Figure 1: CD18-dependent dissemination of invasion-deficient S. typhimurium from the gastrointestinal tract to systemic organs.
Figure 2: CD18-expressing cells of monocyte–macrophage lineage mediate extraintestinal dissemination of invasion-deficient S. typhimurium.
Figure 3: SPI1 invasion genes are required for the elicitation of mucosal but not systemic immune responses to S. typhimurium.
Figure 4: Model for functional and anatomical compartmentalization of the immune response to Salmonella.

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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.

Author information

Author notes

  1. Ruth Berggren

    Present address: Departments of Medicine, Pathology, and Microbiology, University of Colorado Health Sciences Center, Denver, 80262, Colorado, USA

  2. Raphael Valdivia

    Present address: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, 94305, California, USA

  3. Department of Biochemistry, University of California at Berkeley, Berkeley, California 94720, USA (R.V.); Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75325, USA (R.B.).

Authors and Affiliations

  1. Departments of Medicine, Pathology, and Microbiology, University of Colorado Health Sciences Center, Denver, 80262, Colorado, USA

    Andrés Vazquez-Torres, William Brown, Mysan Le & Ferric C. Fang

  2. Department of Immunology, National Jewish Center for Immunology and Respiratory Medicine, Denver, 80262, Colorado, USA

    Jessica Jones-Carson

  3. Department of Medical Microbiology and Immunology, Texas A&M University, College Station, 77843-1114, Texas, USA

    Andreas J. Bäumler

  4. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, 94305, California, USA

    Stanley Falkow

  5. Department of Medicine, Veterans Affairs Medical Center, Denver, 80262, Colorado, USA

    William Brown & Mysan Le

  6. Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, 20892, Maryland, USA

    W. Tony Parks

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  1. Andrés Vazquez-Torres
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Correspondence to Ferric C. Fang.

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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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