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Brain Immune Cell Infiltration and Serum Metabolomic Characteristics Reveal that Lauric Acid Promotes Immune Cell Infiltration in Brain and Streptococcus suis Meningitis in Mice

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Abstract

Although naturally Streptococcus suis serotype 2 (SS2) causes meningitis resulting in death or sequela of neurological symptoms in pigs and humans, severely threatening public health in the world, it has been difficult to build up and confirm experimental meningitis mouse models with obvious neurological syndrome for about two decades, which strongly hampers the in-depth study on the control measures and mechanisms of SS2-induced meningitis. In this study, a typical meningitis mouse model of SS2 was successfully established, as confirmed by the behavioral indicators of balance beam test, suspension test, and gait analysis. With bacteria gathering in the brain, distinguishable unique features including meningeal thickening, vacuolization of the Nissl body, brain barrier damage, glial cell activation, and more infiltration of T cells, macrophages, and DCs are observed in SS2 meningitis mice with typical neurological signs. Some meningitis mice were also accompanied by identical nephritis, ophthalmia, and cochlearitis. Investigation of the metabolic features demonstrated the downregulated cholic acid and upregulated 2-hydroxyvaleric acid, tetrahydrocortisone, nicotinic acid, and lauric acid in blood serum of mice and piglets with meningitis. And feeding trials show that lauric acid can promote meningitis by promoting the infiltration of immune cells into brain. These findings demonstrated that infection of ICR (improved castle road) mice with SS2 was able to induce typical meningitis accompanied by immune cell infiltration and lauric acid upregulation. These data provide a basis for the deep study of SS2 meningitis.

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Funding

This study was supported by the National Key Research and Development Program of China (2021FYD1800405) and the National Natural Science Foundation of China (No. 32072823).

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All authors contributed to the study conception and design. Conceptualization and methodology: Xuan Jiang and Fengyang Li. Formal analysis: Jikun Mei and Tong Wu. Data curation: Junhui Zhu, Ziheng Li, and Zengshuai Wu. Writing—original draft: Xuan Jiang and Hexiang Jiang. Writing—review and editing: Liancheng Lei and Na Li. All authors read and approved the final manuscript.

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Correspondence to Na Li or Liancheng Lei.

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All animal experiments were conducted by the Institutional Animal Care and Committee of Jilin University under the approved protocol number SY202201009 (Date 2021.12.19).

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Jiang, X., Li, F., Mei, J. et al. Brain Immune Cell Infiltration and Serum Metabolomic Characteristics Reveal that Lauric Acid Promotes Immune Cell Infiltration in Brain and Streptococcus suis Meningitis in Mice. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04144-1

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