Meningitic Escherichia coli-Induced Interleukin-17A Facilitates Blood-Brain Barrier Disruption via Inhibiting Proteinase 3/Protease-Activated Receptor 2 Axis

Bojie Xu; Jiaqi Chen; Jiyang Fu; Ruicheng Yang; Bo Yang; Dong Huo; Chen Tan; Huanchun Chen; Xiangru Wang

doi:10.3389/fncel.2022.814867

Meningitic Escherichia coli-Induced Interleukin-17A Facilitates Blood-Brain Barrier Disruption via Inhibiting Proteinase 3/Protease-Activated Receptor 2 Axis

Front Cell Neurosci. 2022 Feb 11:16:814867. doi: 10.3389/fncel.2022.814867. eCollection 2022.

Authors

Bojie Xu^{1

2}, Jiaqi Chen^{1

2}, Jiyang Fu^{1

2}, Ruicheng Yang^{1

2}, Bo Yang^{1

2}, Dong Huo^{1

2}, Chen Tan^{1

2

3

4}, Huanchun Chen^{1

2

3

4}, Xiangru Wang^{1

2

3

4}

Affiliations

¹ State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
² Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.
³ Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People's Republic of China, Wuhan, China.
⁴ International Research Center for Animal Disease, Ministry of Science and Technology of the People's Republic of China, Wuhan, China.

Abstract

Bacterial meningitis is a life-threatening infectious disease with high morbidity and mortality worldwide, among which meningitic Escherichia coli is a common Gram-negative pathogenic bacterium causing meningitis. It can penetrate the blood-brain barrier (BBB), invoke local inflammatory responses and consequently disrupt the integrity of the BBB. Interleukin-17A (IL-17A) is recognized as a pro-inflammatory cytokine that is released during meningitic E. coli infection. It has been reported that IL-17A is involved in several pathological tissue injuries. However, the function of IL-17A in BBB breakdown remains rarely discussed. Here, our study found that E. coli-induced IL-17A led to the degradation of tight junction proteins (TJs) and adherens junction proteins (AJs) in human brain microvascular endothelial cells (hBMECs) through inhibiting protease proteinase 3 (PRTN3)/protease-activated receptor 2 (PAR-2) axis, thus increasing the permeability of BBB. In summary, this study uncovered the involvement of IL-17A in regulating BBB integrity and proposed a novel regulatory mechanism, which could be potential therapeutic targets of E. coli meningitis.

Keywords: Escherichia coli meningitis; IL-17A; PAR-2; PRTN3; blood-brain barrier; permeability.