MicroRNA-302b augments host defense to bacteria by regulating inflammatory responses via feedback to TLR/IRAK4 circuits

Xikun Zhou, Xuefeng Li, Yan Ye, Kelei Zhao, Yan Zhuang, Yi Li, Yuquan Wei and Min Wu ()
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Xikun Zhou: University of North Dakota
Xuefeng Li: University of North Dakota
Yan Ye: University of North Dakota
Kelei Zhao: University of North Dakota
Yan Zhuang: University of North Dakota
Yi Li: University of North Dakota
Yuquan Wei: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University
Min Wu: University of North Dakota

Nature Communications, 2014, vol. 5, issue 1, 1-14

Abstract: Abstract MicroRNAs (miRNAs) have been implicated in a spectrum of physiological and pathological conditions, including immune responses. miR-302b has been implicated in stem cell differentiation but its role in immunity remains unknown. Here we show that miR-302b is induced by Toll-like receptor 2 (TLR2) and TLR4 through ERK-p38-NF-κB signalling upon Gram-negative bacterium Pseudomonas aeruginosa infection. Suppression of inflammatory responses to bacterial infection is mediated by targeting IRAK4, a protein required for the activation and nuclear translocation of NF-κB. Through negative feedback, enforced expression of miR-302b or IRAK4 siRNA silencing inhibits downstream NF-κB signalling and airway leukocyte infiltration, thereby alleviating lung injury and increasing survival in P. aeruginosa-infected mice. In contrast, miR-302b inhibitors exacerbate inflammatory responses and decrease survival in P. aeruginosa-infected mice and lung cells. These findings reveal that miR-302b is a novel inflammatory regulator of NF-κB activation in respiratory bacterial infections by providing negative feedback to TLRs-mediated immunity.

Date: 2014
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DOI: 10.1038/ncomms4619

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