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Interleukin-17A Contributed to the Damage of Blood-CNS Barriers During Streptococcus suis Meningitis

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Abstract

Streptococcus suis (S. suis) is an emerging zoonotic agent that can cause meningitis in humans with high mortality and morbidity. Meningitic S. suis can induce higher level of IL-17 than non-meningitic S. suis. Besides, IL-17A plays various roles on bacterial clearance or disruption of blood-CNS barriers through the downregulation and reorganization of tight junction (TJ) molecules. However, it remains to be elucidated for the role of IL-17A on the infection with meningitic S. suis. Here, we found that meningitic S. suis infection could not only cause acute death due to the damage of multiple organs, but also cause meningitis and clinical nervous signs since 60 h of post-infection due to the penetration of blood-CNS barriers after lasting bacteremia. In contrast, the mice with deficiency of il17a gene could not significantly change the acute inflammatory response and acute death, but it could not show obvious meningitis and clinical nervous signs caused by the meningitic S. suis infection. In addition, we also found that IL-17A could inhibit the transcription and expression of TJ proteins that facilitated the leakage of blood-CNS barriers since 60 h of post-infection during meningitic S. suis infection. Thus, our findings demonstrated that IL-17A could downregulate TJ proteins, which undoubtedly facilitated the leakage of blood-CNS barriers for bacterial invasion and then caused S. suis meningitis, providing potential targets for future prevention and treatment of this disease.

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Acknowledgements

We would like to express our gratitude to Xiang Liu (NIH, USA) for help on discussion of the results.

Funding

This work was supported by the National Natural Science Foundation of China (31772714 and 31972649).

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Authors and Affiliations

  1. State Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, Hubei, China

    Lei Xu, Xi Lu, Peng Xiao, Ran Liu, Kunlong Xia, Meizhou Wu, Meilin Jin & Anding Zhang

  2. Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China

    Lei Xu, Xi Lu, Peng Xiao, Ran Liu, Kunlong Xia, Meizhou Wu, Meilin Jin & Anding Zhang

  3. Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People’s Republic of China, Wuhan, 430070, Hubei, China

    Meilin Jin & Anding Zhang

  4. International Research Center for Animal Disease, Ministry of Science and Technology of the People’s Republic of China, Wuhan, 430070, Hubei, China

    Anding Zhang

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  1. Lei Xu
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Contributions

LX and XL performed the experiments and analyzed the data, AZ and LX drafted the manuscript. PX, RL, and KX helped to analyze the data and revise the manuscript. AZ, MW, and MJ provided the material and technological support. AZ conceived the experiments and revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Anding Zhang.

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All procedures performed in studies involving animals were in accordance with the Scientific Ethics Committee of Huazhong Agricultural University (Permit Number: HZAUMO-2019-048). Consent to participate is not applicable.

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Supplementary Information

ESM 1

Table S1. Quality test results of brain tissue RNA. (XLSX 10 kb)

ESM 2

Fig. S1. Confirmation of il17a-/- mice. a DNA sequencing of the il17a gene in the il17a-/- and il17a+/+ mice. A 23bp DNA sequence was deleted in the il17a-/- mice. b Genotyping by PCR. A 390bp DNA fragment for KO and HET. A 405bp DNA fragment for WT and HET. (TIF 3894 kb)

ESM 3

Fig. S2. Histopathological scores in the brains. Histopathological scores of brain sections from wild type mice at 60h post-infection with meningitic S. suis (n=3). Error bars represented the mean ± standard deviations. (TIF 1425 kb)

ESM 4

Fig. S3. Flow cytometric analysis of Neutrophils isolated from mice blood post-infection. The il17a-/- and il17a+/+ mice were intraperitoneally infected with meningitic S. suis strain S29 or PBS. At the indicated time points, Samples of peripheral blood (0.2 ml) were collected from tail vein and then stained with phycoerythrin (PE) anti-mouse Ly6G and Fluorescein isothiocyanate (FITC) anti-mouse/human CD11b for flow cytometric analysis. Error bars represent the mean ± standard deviations. (TIF 2167 kb)

ESM 5

Fig. S4. Immunofluorescence results of isotype antibody of ZO-1 in brain. The brain of a wild type mouse was analyzed for isotype antibody of ZO-1 via immunofluorescence to exclude unspecific signals. (TIF 3283 kb)

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Xu, L., Lu, X., Xiao, P. et al. Interleukin-17A Contributed to the Damage of Blood-CNS Barriers During Streptococcus suis Meningitis. Mol Neurobiol 59, 2116–2128 (2022). https://doi.org/10.1007/s12035-022-02749-y

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