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The Interplay between Serovar Typhimurium and the Intestinal Mucosa during Oral Infection

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  • Authors: Annika Hausmann1, Wolf-Dietrich Hardt2
  • Editors: Pascale Cossart3, Craig R. Roy4, Philippe Sansonetti5
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Institute of Microbiology, D-BIOL ETH Zurich, Zurich, Switzerland; 2: Institute of Microbiology, D-BIOL ETH Zurich, Zurich, Switzerland; 3: Institut Pasteur, Paris, France; 4: Yale University School of Medicine, New Haven, Connecticut; 5: Institut Pasteur, Paris, France
  • Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0004-2019
  • Received 27 March 2018 Accepted 13 February 2019 Published 05 April 2019
  • Wolf-Dietrich Hardt, [email protected]
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  • Abstract:

    Bacterial infection results in a dynamic interplay between the pathogen and its host. The underlying interactions are multilayered, and the cellular responses are modulated by the local environment. The intestine is a particularly interesting tissue regarding host-pathogen interaction. It is densely colonized by commensal microbes and a portal of entry for ingested pathogens. This necessitates constant monitoring of microbial stimuli in order to maintain homeostasis during encounters with benign microbiota and to trigger immune defenses in response to bacterial pathogens. Homeostasis is maintained by physical barriers (the mucus layer and epithelium), chemical defenses (antimicrobial peptides), and innate immune responses (NLRC4 inflammasome), which keep the bacteria from reaching the sterile lamina propria. Intestinal pathogens represent potent experimental tools to probe these barriers and decipher how pathogens can circumvent them. The streptomycin mouse model of oral serovar Typhimurium infection provides a well-characterized, robust experimental system for such studies. Strikingly, each stage of the gut tissue infection poses a different set of challenges to the pathogen and requires tight control of virulence factor expression, host response modulation, and cooperation between phenotypic subpopulations. Therefore, successful infection of the intestinal tissue relies on a delicate and dynamic balance between responses of the pathogen and its host. These mechanisms can be deciphered to their full extent only in realistic infection models.

  • Citation: Hausmann A, Hardt W. 2019. The Interplay between Serovar Typhimurium and the Intestinal Mucosa during Oral Infection. Microbiol Spectrum 7(2):BAI-0004-2019. doi:10.1128/microbiolspec.BAI-0004-2019.

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/content/journal/microbiolspec/10.1128/microbiolspec.BAI-0004-2019
2019-04-05
2019-06-18

Abstract:

Bacterial infection results in a dynamic interplay between the pathogen and its host. The underlying interactions are multilayered, and the cellular responses are modulated by the local environment. The intestine is a particularly interesting tissue regarding host-pathogen interaction. It is densely colonized by commensal microbes and a portal of entry for ingested pathogens. This necessitates constant monitoring of microbial stimuli in order to maintain homeostasis during encounters with benign microbiota and to trigger immune defenses in response to bacterial pathogens. Homeostasis is maintained by physical barriers (the mucus layer and epithelium), chemical defenses (antimicrobial peptides), and innate immune responses (NLRC4 inflammasome), which keep the bacteria from reaching the sterile lamina propria. Intestinal pathogens represent potent experimental tools to probe these barriers and decipher how pathogens can circumvent them. The streptomycin mouse model of oral serovar Typhimurium infection provides a well-characterized, robust experimental system for such studies. Strikingly, each stage of the gut tissue infection poses a different set of challenges to the pathogen and requires tight control of virulence factor expression, host response modulation, and cooperation between phenotypic subpopulations. Therefore, successful infection of the intestinal tissue relies on a delicate and dynamic balance between responses of the pathogen and its host. These mechanisms can be deciphered to their full extent only in realistic infection models.

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FIGURE 1

Innate defense mechanisms in naive and . Typhimurium (12 h)-infected intestinal mucosa. For efficient infection, . Typhimurium has to overcome several mucosal defense mechanisms. This comprises occupation of the intestinal niche by the microbiota (1) and breaching of the mucus layer (2), the epithelium (3), and physical barriers between the intestinal lumen and the sterile lamina propria (LP) (4, 5). Recognition of intracellular bacteria by PRRs leads to recruitment of immune cells (6) that are able to efficiently kill bacteria and the induction of increased AMP production via immune cells (7). TLR, Toll-like receptor; ILC, innate lymphoid cell; MNP, mononuclear phagocyte; p.i., postinfection.

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0004-2019
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Image of FIGURE 2
FIGURE 2

Different . Typhimurium phenotypes are required at different stages of infection. (a) TTSS-1, flagellum positive, TTSS-2, required for active invasion of host cells; (b) TTSS-1, flagellum negative ( 109 ), TTSS-2, fast growing, ensures transmission; (c) TTSS-1, flagellum negative, TTSS-2, fast growing, intracellular survival; (d) TTSS-1, flagellum negative, TTSS-2, slow growing, antibiotic tolerance (persisters). LP, lamina propria.

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0004-2019
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Tables

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TABLE 1

. Typhimurium virulence factors that modulate the host immune response

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0004-2019
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TABLE 2

Examples of host response-modulating virulence factors of a variety of pathogenic bacteria

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0004-2019

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