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A defined commensal consortium elicits CD8 T cells and anti-cancer immunity

来源:钱柜娱乐注册发布时间:2019/3/1 浏览量:125

takeshi tanoue1,2,3,16, Satoru Morita1,16, Damian r. Plichta4, Ashwin N. Skelly1, Wataru Suda3,5,6, Yuki Sugiura7,Seiko Narushima1,3, Hera Vlamakis4, iori Motoo3, Kayoko Sugita1, Atsushi Shiota1,2, Kozue takeshita1, Keiko Yasuma-Mitobe1,Dieter riethmacher8, tsuneyasu Kaisho9, Jason M. Norman10, Daniel Mucida11, Makoto Suematsu7, tomonori Yaguchi12, Vanni Bucci13, takashi inoue14, Yutaka Kawakami12, Bernat Olle10, Bruce roberts10, Masahira Hattori3,5,6, ramnik J. Xavier4,15,Koji Atarashi1,2,3 & Kenya Honda1,2,3*

Nature 23 January 2019  DOI:10.1038/s41586-019-0878-z

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.

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