title: Innate host defense requires TFEB-mediated transcription of cytoprotective and antimicrobial genes.
abstract: Animal host defense against infection requires the expression of defense genes at the right place and the right time. Understanding such tight control of host defense requires the elucidation of the transcription factors involved. By using an unbiased approach in the model Caenorhabditis elegans, we discovered that HLH-30 (known as TFEB in mammals) is a key transcription factor for host defense. HLH-30 was activated shortly after Staphylococcus aureus infection, and drove the expression of close to 80% of the host response, including antimicrobial and autophagy genes that were essential for host tolerance of infection. TFEB was also rapidly activated in murine macrophages upon S. aureus infection and was required for proper transcriptional induction of several proinflammatory cytokines and chemokines. Thus, our data suggest that TFEB is a previously unappreciated, evolutionarily ancient transcription factor in the host response to infection.
authors.affiliation: Laboratory of Comparative Immunology, Center for the Study of Inflammatory Bowel Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Orane
authors.initials: O
authors.lastname: Visvikis
authors.affiliation: Department of Genetics, Center for Genome Sciences, Washington University Medical School, Saint Louis, Missouri 63118, USA.
authors.forename: Nnamdi
authors.initials: N
authors.lastname: Ihuegbu
authors.affiliation: Laboratory of Comparative Immunology, Center for the Study of Inflammatory Bowel Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Sid A
authors.initials: SA
authors.lastname: Labed
authors.affiliation: Laboratory of Comparative Immunology, Center for the Study of Inflammatory Bowel Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Lyly G
authors.initials: LG
authors.lastname: Luhachack
authors.affiliation: Laboratory of Comparative Immunology, Center for the Study of Inflammatory Bowel Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Anna-Maria F
authors.initials: AF
authors.lastname: Alves
authors.affiliation: Laboratory of Comparative Immunology, Center for the Study of Inflammatory Bowel Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Wollenberg
authors.affiliation: Bill and Melinda Gates Foundation, Seattle, Washington 98109, USA.
authors.forename: Lynda M
authors.initials: LM
authors.lastname: Stuart
authors.affiliation: Department of Genetics, Center for Genome Sciences, Washington University Medical School, Saint Louis, Missouri 63118, USA.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Stormo
authors.affiliation: Laboratory of Comparative Immunology, Center for the Study of Inflammatory Bowel Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Javier E
authors.initials: JE
authors.lastname: Irazoqui
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000276:immunology; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000276:immunology*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000276:immunology*; D017173:Caenorhabditis elegans / Q000276:immunology* / Q000382:microbiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000276:immunology*; D013293:Enterococcus faecalis / Q000276:immunology; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology; D051379:Mice; D011552:Pseudomonas Infections / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000276:immunology; D034622:RNA Interference; D034741:RNA, Small Interfering; D012480:Salmonella Infections / Q000276:immunology; D019779:Salmonella enterica / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology; D015533:Transcriptional Activation / Q000235:genetics / Q000276:immunology
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D029742:Caenorhabditis elegans Proteins; D034741:RNA, Small Interfering; C583069:HLH-30 protein, C elegans; C484068:Tcfeb protein, mouse