Reference - Detail
| RRC ID | 45871 |
|---|---|
| Author | Visvikis O, Ihuegbu N, Labed SA, Luhachack LG, Alves AF, Wollenberg AC, Stuart LM, Stormo GD, Irazoqui JE. |
| Title | Innate host defense requires TFEB-mediated transcription of cytoprotective and antimicrobial genes. |
| Journal | Immunity |
| 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. |
| Volume | 40(6) |
| Pages | 896-909 |
| Published | 2014-6-19 |
| DOI | 10.1016/j.immuni.2014.05.002 |
| PMID | 24882217 |
| PMC | PMC4104614 |
| MeSH | Animals Autophagy / genetics Autophagy / immunology Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / immunology* Basic Helix-Loop-Helix Transcription Factors / genetics Basic Helix-Loop-Helix Transcription Factors / immunology* Caenorhabditis elegans / immunology* Caenorhabditis elegans / microbiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / immunology* Enterococcus faecalis / immunology Immunity, Innate Macrophages / immunology Mice Pseudomonas Infections / immunology Pseudomonas aeruginosa / immunology RNA Interference RNA, Small Interfering Salmonella Infections / immunology Salmonella enterica / immunology Signal Transduction / immunology Staphylococcal Infections / immunology* Staphylococcus aureus / immunology Transcriptional Activation / genetics Transcriptional Activation / immunology |
| IF | 22.553 |
| Times Cited | 114 |
| WOS Category | IMMUNOLOGY |
| Resource | |
| C.elegans | tm1978 |