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No vacancy: how beneficial microbes cooperate with immunity to provide colonization resistance to pathogens - PubMed

  • ️Thu Jan 01 2015

Review

No vacancy: how beneficial microbes cooperate with immunity to provide colonization resistance to pathogens

Martina Sassone-Corsi et al. J Immunol. 2015.

Abstract

The mammalian intestine harbors a community of trillions of microbes, collectively known as the gut microbiota, which coevolved with the host in a mutually beneficial relationship. Among the numerous gut microbial species, certain commensal bacteria are known to provide health benefits to the host when administered in adequate amounts and, as such, are labeled "probiotics." We review some of the mechanisms by which probiotics and other beneficial commensals provide colonization resistance to pathogens. The battle for similar nutrients and the bacterial secretion of antimicrobials provide a direct means of competition between beneficial and harmful microbes. Beneficial microbes can also indirectly diminish pathogen colonization by stimulating the development of innate and adaptive immunity, as well as the function of the mucosal barrier. Altogether, we gather and present evidence that beneficial microbes cooperate with host immunity in an effort to shut out pathogens.

Copyright © 2015 by The American Association of Immunologists, Inc.

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Figures

Figure 1
Figure 1. Direct mechanisms of colonization resistance against enteropathogens

The microbiota provide a barrier against incoming enteric pathogens via multiple mechanisms. (1) Adhesion exclusion: Certain commensals reduce pathogen adherence to the intestinal mucosa. (2) Carbon source limitation: Human commensal Escherichia coli strain HS and probiotic strain Escherichia coli Nissle 1917 both metabolize multiple sugar molecules, which limits the availability of nutrients in the gut to certain pathogens. (3) Micronutrient limitation: The probiotic strain E. coli Nissle 1917 can uptake iron via several mechanisms, limiting its availability to pathogens such as Salmonella Typhimurium. (4) Secretion of antimicrobials: Commensals act against pathogens not only by limiting nutrients, but also by the production antimicrobial compounds, such as bacteriocins and microcins. (5) Direct delivery of toxins: Although not yet demonstrated in vivo, commensals can express type 6-secretion systems (T6SSs) and contact-dependent inhibition (CDI) systems, means by which to deliver growth-inhibiting toxins to close competitors. (6) Circumventing colonization resistance: Pathogens employ a variety of virulence factors to colonize the host and cause disease.

Figure 2
Figure 2. Microbiota-stimulated host immunity provides colonization resistance

Commensal bacteria can indirectly control pathogen colonization by a variety of means. (1) Barrier function: The commensal microbiota up-regulates host barrier function by contributing to the development of the mucus layer. (2) Short-chain fatty acid (SCFA) production: Members of the microbiota such as Bifidobacterium spp. can enhance epithelial barrier function by producing SCFAs such as acetate. (3) IL-1β-mediated neutrophil recruitment: Commensals can promote protection against certain pathogens by stimulating IL-1β processing and secretion, resulting in the recruitment of neutrophils to the site of the infection. (4) IL-22-dependent release of antimicrobials: Certain commensals (such as Lactobacillus reuteri) induce the secretion of IL-22 by innate lymphoid cells (ILCs), which can in turn protect against some pathogens via the induction of antimicrobial release by epithelial cells. (5) Direct stimulation of antimicrobial production by the host: Secretion of antimicrobial proteins (AMPs), including α-defensins and REG3γ, is a key component in controlling pathogen growth, and is in part mediated by commensal-dependent mechanisms. (6) Induction of T cell differentiation: Commensals can promote adaptive immunity by inducing the differentiation of T cells, such as by stimulating Th17 and Treg cell differentiation and activation. (7) Secretory IgA (sIgA): Commensals can facilitate host-barrier function by inducing B cells and by regulating the secretion of IgA.

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