Enhancing mucosal immunity by transient microbiota depletion

Simone Becattini (), Eric R. Littmann, Ruth Seok, Luigi Amoretti, Emily Fontana, Roberta Wright, Mergim Gjonbalaj, Ingrid M. Leiner, George Plitas, Tobias M. Hohl and Eric G. Pamer
Additional contact information
Simone Becattini: Memorial Sloan Kettering Cancer Center
Eric R. Littmann: Memorial Sloan Kettering Cancer Center
Ruth Seok: Memorial Sloan Kettering Cancer Center
Luigi Amoretti: Memorial Sloan Kettering Cancer Center
Emily Fontana: Memorial Sloan Kettering Cancer Center
Roberta Wright: Memorial Sloan Kettering Cancer Center
Mergim Gjonbalaj: Memorial Sloan Kettering Cancer Center
Ingrid M. Leiner: Memorial Sloan Kettering Cancer Center
George Plitas: Memorial Sloan Kettering Cancer Center
Tobias M. Hohl: Memorial Sloan Kettering Cancer Center
Eric G. Pamer: Memorial Sloan Kettering Cancer Center

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18248-4

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DOI: 10.1038/s41467-020-18248-4

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