TY - JOUR
T1 - Innate host defense requires TFEB-mediated transcription of cytoprotective and antimicrobial genes
AU - Visvikis, Orane
AU - Ihuegbu, Nnamdi
AU - Labed, Sid A.
AU - Luhachack, Lyly G.
AU - Alves, Anna Maria F.
AU - Wollenberg, Amanda C.
AU - Stuart, Lynda M.
AU - Stormo, Gary D.
AU - Irazoqui, Javier E.
N1 - Funding Information:
We thank A. Lacy-Hulbert for helpful discussions, S. Margolis for critical reading of the manuscript, A. Sokolovska and A. Tanne for assistance with macrophage experiments, L.R. Lapierre and M. Hansen for sharing unpublished data, M. Ferron and G. Karsenty for their generous gift of TFEB-3xFLAG RAW264.7 cells, and V. Ambros for the hlh-30(tm1978) strain. We thank the Genome Access Technology Center at Washington University Medical School for their sequencing assistance, especially N. Rockweiler for helpful discussions. Some C. elegans strains were provided by the Caenorhabditis Genetics Center, which is funded by the NIH Office of Research Infrastructure Programs (P40-OD010440). This study was funded in part by the National Institute of General Medical Sciences of the National Institutes of Health, under awards numbers P30-GM092431, R01-GM101056, and R01-GM101056-S1 (to J. E. I.) and R01-HG000249 from the NHGRI (to G. D. S.). O.V. was funded by a Fund for Medical Discovery postdoctoral fellowship from the Massachusetts General Hospital.
PY - 2014/6/19
Y1 - 2014/6/19
N2 - 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 apreviously unappreciated, evolutionarily ancient transcription factor in the host response to infection.
AB - 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 apreviously unappreciated, evolutionarily ancient transcription factor in the host response to infection.
UR - http://www.scopus.com/inward/record.url?scp=84902658412&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2014.05.002
DO - 10.1016/j.immuni.2014.05.002
M3 - Article
C2 - 24882217
AN - SCOPUS:84902658412
SN - 1074-7613
VL - 40
SP - 896
EP - 909
JO - Immunity
JF - Immunity
IS - 6
ER -