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An Evolutionarily Conserved PLC-PKD-TFEB Pathway for Host Defense.

ABSTRACT: The mechanisms that tightly control the transcription of host defense genes have not been fully elucidated. We previously identified TFEB as a transcription factor important for host defense, but the mechanisms that regulate TFEB during infection remained unknown. Here, we used C. elegans to discover a pathway that activates TFEB during infection. Gene dkf-1, which encodes a homolog of protein kinase D (PKD), was required for TFEB activation in nematodes infected with Staphylococcus aureus. Conversely, pharmacological activation of PKD was sufficient to activate TFEB. Furthermore, phospholipase C (PLC) gene plc-1 was also required for TFEB activation, downstream of G?q homolog egl-30 and upstream of dkf-1. Using reverse and chemical genetics, we discovered a similar PLC-PKD-TFEB axis in Salmonella-infected mouse macrophages. In addition, PKC? was required in macrophages. These observations reveal a previously unknown host defense signaling pathway, which has been conserved across one billion years of evolution.

SUBMITTER: Najibi M

PROVIDER: S-EPMC4880541 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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An Evolutionarily Conserved PLC-PKD-TFEB Pathway for Host Defense.

Najibi Mehran M Labed Sid Ahmed SA Visvikis Orane O Irazoqui Javier Elbio JE

Cell reports 20160512 8

The mechanisms that tightly control the transcription of host defense genes have not been fully elucidated. We previously identified TFEB as a transcription factor important for host defense, but the mechanisms that regulate TFEB during infection remained unknown. Here, we used C. elegans to discover a pathway that activates TFEB during infection. Gene dkf-1, which encodes a homolog of protein kinase D (PKD), was required for TFEB activation in nematodes infected with Staphylococcus aureus. Conv ...[more]

PMID: 27184844

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