Enhancing mucosal immunity by transient microbiota depletion
Authors: Simone Becattini, Eric R. Littmann, Ruth Seok, Luigi Amoretti, Emily Fontana, Roberta Wright, Mergim Gjonbalaj, Ingrid M. Leiner, George Plitas, Tobias M. Hohl & Eric G. Pamer
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.
Reference: Becattini, S., Littmann, E.R., Seok, R. et al. Enhancing mucosal immunity by transient microbiota depletion. Nat Commun 11, 4475 (2020). https://doi.org/10.1038/s41467-020-18248-4