title: Diverse intracellular pathogens activate type III interferon expression from peroxisomes.
abstract: Type I interferon responses are considered the primary means by which viral infections are controlled in mammals. Despite this view, several pathogens activate antiviral responses in the absence of type I interferons. The mechanisms controlling type I interferon-independent responses are undefined. We found that RIG-I like receptors (RLRs) induce type III interferon expression in a variety of human cell types, and identified factors that differentially regulate expression of type I and type III interferons. We identified peroxisomes as a primary site of initiation of type III interferon expression, and revealed that the process of intestinal epithelial cell differentiation upregulates peroxisome biogenesis and promotes robust type III interferon responses in human cells. These findings highlight the importance of different intracellular organelles in specific innate immune responses.
authors: Harvard Medical School and Division of Gastroenterology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors: Charlotte
authors: C
authors: Odendall
authors: 1] Harvard Medical School and Division of Gastroenterology, Boston Children's Hospital, Boston, Massachusetts, USA. [2].
authors: Evelyn
authors: E
authors: Dixit
authors: 1] Institut Pasteur, Unité des Interactions Bactéries Cellules, Institut National de la Santé et de la Recherche Médicale U604, Institut national de la recherche agronomique (INRA) USC2020, Paris, France. [2].
authors: Fabrizia
authors: F
authors: Stavru
authors: 1] Institut Pasteur, Unité des Interactions Bactéries Cellules, Institut National de la Santé et de la Recherche Médicale U604, Institut national de la recherche agronomique (INRA) USC2020, Paris, France. [2].
authors: Helene
authors: H
authors: Bierne
authors: Harvard Medical School and Division of Gastroenterology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors: Kate M
authors: KM
authors: Franz
authors: 1] Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA. [2] Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Ann Fiegen
authors: AF
authors: Durbin
authors: Department of Infectious Diseases, Virology Schaller research group at CellNetworks and Deutsches Krebsforschungszentrum (DKFZ), University of Heidelberg, Heidelberg, Germany.
authors: Steeve
authors: S
authors: Boulant
authors: 1] Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA. [2] Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Lee
authors: L
authors: Gehrke
authors: Institut Pasteur, Unité des Interactions Bactéries Cellules, Institut National de la Santé et de la Recherche Médicale U604, Institut national de la recherche agronomique (INRA) USC2020, Paris, France.
authors: Pascale
authors: P
authors: Cossart
authors: Harvard Medical School and Division of Gastroenterology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors: Jonathan C
authors: JC
authors: Kagan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D003510:Cyclohexanes / Q000494:pharmacology; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons / Q000096:biosynthesis / Q000276:immunology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics; D051379:Mice; D020675:Peroxisomes / Q000276:immunology*; D011728:Pyridones / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; D012087:Reoviridae / Q000276:immunology; D012088:Reoviridae Infections / Q000276:immunology; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D020032:Tyrphostins / Q000494:pharmacology; D014740:Vidarabine / Q000031:analogs & derivatives / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: C500162:1,2,3,4,5,6-hexabromocyclohexane; C524063:2-tert-butyl-9-fluoro-3,6-dihydro-7H-benz(h)imidazo(4,5-f)isoquinoline-7-one; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D003510:Cyclohexanes; D004791:Enzyme Inhibitors; D011728:Pyridones; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D007372:Interferons; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D048051:p38 Mitogen-Activated Protein Kinases; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D014740:Vidarabine; C024352:fludarabine