A defined commensal consortium elicits CD8 T cells and anti-cancer immunity
| Autor: | Satoru Morita, Takeshi Tanoue, Kozue Takeshita, Yutaka Kawakami, Ashwin N. Skelly, Hera Vlamakis, Jason M. Norman, Kenya Honda, Makoto Suematsu, Bernat Olle, Vanni Bucci, Tomonori Yaguchi, Takashi Inoue, Koji Atarashi, Masahira Hattori, Iori Motoo, Keiko Yasuma-Mitobe, Daniel Mucida, Seiko Narushima, Bruce L. Roberts, Dieter Riethmacher, Ramnik J. Xavier, Atsushi Shiota, Damian R. Plichta, Yuki Sugiura, Wataru Suda, Kayoko Sugita, Tsuneyasu Kaisho |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Programmed Cell Death 1 Receptor Inflammation Adenocarcinoma CD8-Positive T-Lymphocytes Gut flora Major histocompatibility complex Microbiology Feces Interferon-gamma Mice 03 medical and health sciences 0302 clinical medicine Antigen Antigens CD Cell Line Tumor medicine Animals Humans Cytotoxic T cell Listeriosis Microbiome Symbiosis Multidisciplinary Bacteria biology Histocompatibility Antigens Class I Human microbiome Dendritic Cells biology.organism_classification Listeria monocytogenes Xenograft Model Antitumor Assays Healthy Volunteers Gastrointestinal Microbiome 030104 developmental biology Mucosal immunology 030220 oncology & carcinogenesis biology.protein Female medicine.symptom Integrin alpha Chains |
| Zdroj: | Nature. 565:600-605 |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/s41586-019-0878-z |
| Popis: | 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. A consortium of 11 bacterial strains from the healthy human gut microbiota can strongly induce interferon-γ-producing CD8 T cells in the intestine, and enhance both resistance to bacterial infection and the therapeutic efficacy of immune checkpoint inhibitors. |
| Databáze: | OpenAIRE |
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