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Microbial recognition by GEF-H1 controls IKK? mediated activation of IRF5.

ABSTRACT: During infection, transcription factor interferon regulatory factor 5 (IRF5) is essential for the control of host defense. Here we show that the microtubule-associated guanine nucleotide exchange factor (GEF)-H1, is required for the phosphorylation of IRF5 by microbial muramyl-dipeptides (MDP), the minimal structural motif of peptidoglycan of both Gram-positive and Gram-negative bacteria. Specifically, GEF-H1 functions in a microtubule based recognition system for microbial peptidoglycans that mediates the activation of IKK? which we identify as a new upstream IKK?/? and IRF5 kinase. The deletion of GEF-H1 or dominant-negative variants of GEF-H1 prevent activation of IKK? and phosphorylation of IRF5. The GEF-H1-IKK?-IRF5 signaling axis functions independent of NOD-like receptors and is critically required for the recognition of intracellular peptidoglycans and host defenses against Listeria monocytogenes.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC6430831 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Microbial recognition by GEF-H1 controls IKKε mediated activation of IRF5.

Zhao Yun Y Zagani Rachid R Park Sung-Moo SM Yoshida Naohiro N Shah Pankaj P Reinecker Hans-Christian HC

Nature communications 20190322 1

During infection, transcription factor interferon regulatory factor 5 (IRF5) is essential for the control of host defense. Here we show that the microtubule-associated guanine nucleotide exchange factor (GEF)-H1, is required for the phosphorylation of IRF5 by microbial muramyl-dipeptides (MDP), the minimal structural motif of peptidoglycan of both Gram-positive and Gram-negative bacteria. Specifically, GEF-H1 functions in a microtubule based recognition system for microbial peptidoglycans that m ...[more]

PMID: 30902986

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