Enhancing mucosal immunity by transient microbiota depletion Journal Article

Authors: Becattini, S.; Littmann, E. R.; Seok, R.; Amoretti, L.; Fontana, E.; Wright, R.; Gjonbalaj, M.; Leiner, I. M.; Plitas, G.; Hohl, T. M.; Pamer, E. G.
Article Title: 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. © 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
Journal Title: Nature Communications
Volume: 11
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2020-09-08
Start Page: 4475
Language: English
DOI: 10.1038/s41467-020-18248-4
PUBMED: 32901029
PROVIDER: scopus
PMCID: PMC7479140
Notes: Article -- Source: Scopus
Citation Impact
MSK Authors
  1. Tobias Martin Hohl
    83 Hohl
  2. Eric Pamer
    278 Pamer
  3. George Plitas
    83 Plitas
  4. Ingrid Leiner
    49 Leiner
  5. Emily Fontana
    24 Fontana
  6. Ruth Seok
    6 Seok
  7. Roberta Justine Wright
    12 Wright