| 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. © 2020, The Author(s). |
| Keywords: |
cd8+ t lymphocyte; cd8-positive t-lymphocytes; mouse; animal; animals; mice; mice, knockout; drug effect; mice, inbred c57bl; c57bl mouse; growth, development and aging; immunology; antigen; chemotaxis; antigens; vaccination; immunity; memory; intestine flora; administration, oral; immunologic memory; listeria monocytogenes; knockout mouse; colonization; oral drug administration; microorganism; immunological memory; antibiotics; streptomycin; pathogen; ovalbumin; immunity, mucosal; mucosal immunity; cell component; female; gastrointestinal microbiome; host microbial interactions
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