title: Interferon-λ and interleukin 22 act synergistically for the induction of interferon-stimulated genes and control of rotavirus infection.
abstract: The epithelium is the main entry point for many viruses, but the processes that protect barrier surfaces against viral infections are incompletely understood. Here we identified interleukin 22 (IL-22) produced by innate lymphoid cell group 3 (ILC3) as an amplifier of signaling via interferon-λ (IFN-λ), a synergism needed to curtail the replication of rotavirus, the leading cause of childhood gastroenteritis. Cooperation between the receptor for IL-22 and the receptor for IFN-λ, both of which were 'preferentially' expressed by intestinal epithelial cells (IECs), was required for optimal activation of the transcription factor STAT1 and expression of interferon-stimulated genes (ISGs). These data suggested that epithelial cells are protected against viral replication by co-option of two evolutionarily related cytokine networks. These data may inform the design of novel immunotherapy for viral infections that are sensitive to interferons.
authors.affiliation: Research Centre Immunology and Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67, D-55131 Mainz, Germany.|Department of Medical Microbiology and Hygiene, Institute for Medical Microbiology and Hygiene, Freiburg University Medical Centre, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany.|Max-Planck-Institute for Immunobiology and Epigenetics, Stübeweg 51, D-79108 Freiburg, Germany.
authors.forename: Pedro P
authors.initials: PP
authors.lastname: Hernández
authors.affiliation: Department of Medical Microbiology and Hygiene, Institute for Virology, Freiburg University Medical Centre, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany.|Spemann Graduate School of Biology and Medicine, University of Freiburg, Albertstrasse 19A, D-79104 Freiburg, Germany.
authors.forename: Tanel
authors.initials: T
authors.lastname: Mahlakoiv
authors.affiliation: Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany and DZIF - German Center for Infection Research, Hannover-Braunschweig Site, D-30625 Hannover, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Yang
authors.affiliation: Research Centre Immunology and Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67, D-55131 Mainz, Germany.|Department of Medical Microbiology and Hygiene, Institute for Medical Microbiology and Hygiene, Freiburg University Medical Centre, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Schwierzeck
authors.affiliation: Department of Medical Microbiology and Hygiene, Institute for Medical Microbiology and Hygiene, Freiburg University Medical Centre, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany.
authors.forename: Nam
authors.initials: N
authors.lastname: Nguyen
authors.affiliation: Research Centre Immunology and Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67, D-55131 Mainz, Germany.|Department of Medical Microbiology and Hygiene, Institute for Medical Microbiology and Hygiene, Freiburg University Medical Centre, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany.|Research Training Group (GRK1104) of Organogenesis, Hauptstrasse 1, D-79104 Freiburg, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Guendel
authors.affiliation: Research Centre Immunology and Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67, D-55131 Mainz, Germany.|Department of Medical Microbiology and Hygiene, Institute for Medical Microbiology and Hygiene, Freiburg University Medical Centre, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany.|Max-Planck-Institute for Immunobiology and Epigenetics, Stübeweg 51, D-79108 Freiburg, Germany.
authors.forename: Konrad
authors.initials: K
authors.lastname: Gronke
authors.affiliation: INEM - UMR7355, Molecular Immunology, University and CNRS, F-45071 Orleans, France and Institute of Infectious Disease, University of Cape Town, RSA.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.affiliation: Infection Immunology Research, Research Center Borstel, D-23845 Borstel, Germany.|Cluster of Excellence Inflammation at Interfaces (Borstel-Kiel-Lübeck-Plön).
authors.forename: Christoph
authors.initials: C
authors.lastname: Hoelscher
authors.affiliation: Ludwig Institute for Cancer Research, Université Catholique de Louvain, 74 Avenue Hippocrate, B-1200 Brussels, Belgium.
authors.forename: Laure
authors.initials: L
authors.lastname: Dumoutier
authors.affiliation: Ludwig Institute for Cancer Research, Université Catholique de Louvain, 74 Avenue Hippocrate, B-1200 Brussels, Belgium.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Renauld
authors.affiliation: Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany and DZIF - German Center for Infection Research, Hannover-Braunschweig Site, D-30625 Hannover, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Suerbaum
authors.affiliation: Department of Medical Microbiology and Hygiene, Institute for Virology, Freiburg University Medical Centre, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Staeheli
authors.affiliation: Research Centre Immunology and Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Obere Zahlbacher Strasse 67, D-55131 Mainz, Germany.|Department of Medical Microbiology and Hygiene, Institute for Medical Microbiology and Hygiene, Freiburg University Medical Centre, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany.|Research Training Group (GRK1104) of Organogenesis, Hauptstrasse 1, D-79104 Freiburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Diefenbach
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D004285:Dogs; D004357:Drug Synergism; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology*; D019073:HT29 Cells; D006801:Humans; D015151:Immunoblotting; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology / Q000821:virology; D061985:Madin Darby Canine Kidney Cells; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012400:Rotavirus Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014709:Vero Cells; D000097043:Interleukin-22; D000095022:Interferon Lambda
chemical_list: D016207:Cytokines; D007378:Interleukins; D018121:Receptors, Cytokine; D050794:STAT1 Transcription Factor; D000097043:Interleukin-22; C511668:interferon-lambda protein, mouse; D000095022:Interferon Lambda