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Abstract

There is a growing appreciation for the importance of the gut microbiota as a therapeutic target in various diseases. However, there are only a handful of known commensal strains that can potentially be used to manipulate host physiological functions. Here we isolate a consortium of 11 bacterial strains from healthy human donor faeces that is capable of robustly inducing interferon-γ-producing CD8 T cells in the intestine. These 11 strains act together to mediate the induction without causing inflammation in a manner that is dependent on CD103+ dendritic cells and major histocompatibility (MHC) class Ia molecules. Colonization of mice with the 11-strain mixture enhances both host resistance against Listeria monocytogenes infection and the therapeutic efficacy of immune checkpoint inhibitors in syngeneic tumour models. The 11 strains primarily represent rare, low-abundance components of the human microbiome, and thus have great potential as broadly effective biotherapeutics.

Details

Title
A defined commensal consortium elicits CD8 T cells and anti-cancer immunity
Author
Tanoue, Takeshi 1 ; Morita, Satoru 1 ; Plichta, Damian R 2 ; Skelly, Ashwin N 1 ; Suda, Wataru 3 ; Sugiura, Yuki; Narushima, Seiko; Vlamakis, Hera; Motoo, Iori; Sugita, Kayoko; Shiota, Atsushi; Takeshita, Kozue; Yasuma-Mitobe, Keiko; Riethmacher, Dieter; Kaisho, Tsuneyasu; Norman, Jason M; Mucida, Daniel; Suematsu, Makoto; Yaguchi, Tomonori; Bucci, Vanni; Inoue, Takashi; Kawakami, Yutaka; Olle, Bernat; Roberts, Bruce; Hattori, Masahira; Xavier, Ramnik J; Atarashi, Koji; Honda, Kenya

 Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan 
 Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA 
 RIKEN Center for Integrative Medical Sciences, Yokohama, Japan 
Pages
600-4,605A-605O
Section
ARTICLE
Publication year
2019
Publication date
Jan 31, 2019
Publisher
Nature Publishing Group
ISSN
00280836
e-ISSN
14764687
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2178519865
Copyright
Copyright Nature Publishing Group Jan 31, 2019