Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes

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

doi:10.1038/44593

Cited by 683Salmonella and Campylobacter epidemiologyEscherichia coli research studiesImmune Response and Inflammation

Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes

Vazquez-Torres, Andrés, Jones-Carson, Jessica, Bäumler, Andreas J., Falkow, Stanley, Valdivia, Raphael, Brown, William, Le, Mysan, Berggren, Ruth +2 more·1999·Nature

DOI 10.1038/44593

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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.

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S.Tm survives inside MPS cells such as spleen and liver macrophages, causes systemic disease in mice, and is known to require iron.
“This Gram-negative bacterium persists within MPS cells, including spleen and liver macrophages, it causes systemic disease in mice (Vazquez-Torres et al., 1999, 2004), and its dependence on iron is well established (Nairz et al., 2007).”
From Iron Regulatory Proteins Mediate Host Resistance to Salmonella Infection (2015) · cites this paper as Vazquez-Torres et al., 1999
Salmonella Typhimurium needs sufficient access to host iron resources as a prerequisite for replication and virulence.
“Salmonella Typhimurium, a facultative intracellular microbe, needs to gain sufficient access to host iron resources as a prerequisite for replication and virulence (Leung and Finlay, 1991; Vazquez-Torres et al., 1999).”
From Genetic and Dietary Iron Overload Differentially Affect the Course of Salmonella Typhimurium Infection (2017) · cites this paper as Vazquez-Torres et al., 1999

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Authors: Vazquez-Torres, A., Jones-Carson, J., Bäumler, A. J., Falkow, S., Valdivia, R., Brown, W., Le, M., Berggren, R., Parks, W. T., & Fang, F. C.
Affiliations: Texas A&M University (US)
Stanford Medicine (US)
University of California, Berkeley (US)
Denver VA Medical Center (US)
The University of Texas Southwestern Medical Center (US)
National Institutes of Health (US)
University of Colorado Denver (US)
Corresponding author: Fang, Ferric C.
ORCID: Bäumler, Andreas J.
Valdivia, Raphael
Parks, W. Tony
Fang, Ferric C.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1999-10
Volume: 401
Issue: 6755
Pages: 804-808
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/44593
OpenAlex: W1649341603
Cited by: 683
References: 31
Citations by year: 2026: 8 · 2025: 19 · 2024: 19 · 2023: 17 · 2022: 17 · 2021: 29 · 2020: 25 · 2019: 26 · 2018: 20 · 2017: 21 · 2016: 24 · 2015: 28 · 2014: 28 · 2013: 23 · 2012: 28
FWCI: 46.32
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: National Institute of Allergy and Infectious Diseases (R01AI044486)
Topics: Life Sciences › Agricultural and Biological Sciences › Food Science › Salmonella and Campylobacter epidemiology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: Salmonella typhimurium, extraintestinal dissemination, CD18, phagocytes, Peyer's patches, M cells, Salmonella pathogenicity island 1, oral infection, systemic immunity, humoral immune response, IgG, spleen, liver, mucosal IgA
MeSH terms: Animals, Bacterial Proteins, Biological Transport, Genes, Bacterial, Intestinal Mucosa, Intestines, Mice, Inbred C57BL, Phagocytes, Fimbriae, Bacterial, Salmonella Infections, Animal, Salmonella typhimurium, Mutagenesis, Bacteremia, CD18 Antigens, Immunity, Mucosal, Alkyl and Aryl Transferases, 3-Phosphoshikimate 1-Carboxyvinyltransferase, Mice

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Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes

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