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Enhancing mucosal immunity by transient microbiota depletion.

ABSTRACT: Tissue resident memory CD8+?T cells (Trm) are poised for immediate reactivation at sites of pathogen entry and provide optimal protection of mucosal surfaces. The intestinal tract represents a portal of entry for many infectious agents; however, to date specific strategies to enhance Trm responses at this site are lacking. Here, we present TMDI (Transient Microbiota Depletion-boosted Immunization), an approach that leverages antibiotic treatment to temporarily restrain microbiota-mediated colonization resistance, and favor intestinal expansion to high densities of an orally-delivered Listeria monocytogenes strain carrying an antigen of choice. By augmenting the local chemotactic gradient as well as the antigenic load, this procedure generates a highly expanded pool of functional, antigen-specific intestinal Trm, ultimately enhancing protection against infectious re-challenge in mice. We propose that TMDI is a useful model to dissect the requirements for optimal Trm responses in the intestine, and also a potential platform to devise novel mucosal vaccination approaches.

SUBMITTER: Becattini S

PROVIDER: S-EPMC7479140 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Enhancing mucosal immunity by transient microbiota depletion.

Becattini Simone S Littmann Eric R ER Seok Ruth R Amoretti Luigi L Fontana Emily E Wright Roberta R Gjonbalaj Mergim M Leiner Ingrid M IM Plitas George G Hohl Tobias M TM Pamer Eric G EG

Nature communications 20200908 1

Tissue resident memory CD8<sup>+</sup> T cells (Trm) are poised for immediate reactivation at sites of pathogen entry and provide optimal protection of mucosal surfaces. The intestinal tract represents a portal of entry for many infectious agents; however, to date specific strategies to enhance Trm responses at this site are lacking. Here, we present TMDI (Transient Microbiota Depletion-boosted Immunization), an approach that leverages antibiotic treatment to temporarily restrain microbiota-medi ...[more]

PMID: 32901029

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Enhancing mucosal immunity by transient microbiota depletion.

Publications

Enhancing mucosal immunity by transient microbiota depletion.

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