Format

Send to

Choose Destination
See comment in PubMed Commons below
Immunity. 2014 Jun 19;40(6):896-909. doi: 10.1016/j.immuni.2014.05.002. Epub 2014 May 29.

Innate host defense requires TFEB-mediated transcription of cytoprotective and antimicrobial genes.

Author information

1
Laboratory of Comparative Immunology, Center for the Study of Inflammatory Bowel Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
2
Department of Genetics, Center for Genome Sciences, Washington University Medical School, Saint Louis, Missouri 63118, USA.
3
Bill and Melinda Gates Foundation, Seattle, Washington 98109, USA.
#
Contributed equally

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.

PMID:
24882217
PMCID:
PMC4104614
DOI:
10.1016/j.immuni.2014.05.002
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Secondary source ID, Grant support

Publication types

MeSH terms

Substances

Secondary source ID

Grant support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for PubMed Central
    Loading ...
    Support Center