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Enhancing mucosal immunity by transient microbiota depletion

Littmann, Eric R
Seok, Ruth
Amoretti, Luigi
Fontana, Emily
Wright, Roberta
Gjonbalaj, Mergim
Leiner, Ingrid M
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Published in Nature communications. 2020, vol. 11, no. 1, 4475
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.
Keywords Administration, OralAnimalsAntigens/administration & dosageCD8-Positive T-Lymphocytes/immunologyChemotaxis/immunologyFemaleGastrointestinal Microbiome/drug effects/immunologyHost Microbial Interactions/immunologyImmunity, Mucosal/drug effectsImmunologic MemoryListeria monocytogenes/growth & development/immunologyMiceMice, Inbred C57BLMice, KnockoutOvalbumin/administration & dosageStreptomycin/administration & dosage
PMID: 32901029
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Research group Groupe Simone Becattini (1027)
FNS: P2EZP3_159083
Autre: NIH grants AI042135 and P30 CA008748
(ISO format)
BECATTINI, Simone et al. Enhancing mucosal immunity by transient microbiota depletion. In: Nature Communications, 2020, vol. 11, n° 1, p. 4475. doi: 10.1038/s41467-020-18248-4

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Deposited on : 2020-11-18

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