Increased expression of the kynurenine pathway in mice with eosinophilic meningitis caused by Angiostrongylus cantonensis infection

• Published in: Acta tropica Vol. 256; p. 107251
• Main Authors: Tsai, Hung-Chin, Chen, Yu-Hsin, Jen, Jing-Yueh, Chang, Hui-Min
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2024
• Subjects: Angiostrongylus cantonensis; Dexamethasone; Eosinophilic meningitis; Kynurenine pathway; Eosinophilic meningitis; Dexamethasone; Angiostrongylus cantonensis; Kynurenine pathway
• ISSN: 0001-706X; 1873-6254; 1873-6254
• DOI: 10.1016/j.actatropica.2024.107251

•A. cantonensis infection inducing blood brain barrier damage, then increased the influx of tryptophan into CSF.•An imbalance of kynurenine pathway may be related to parasitic eosinophilic meningitis caused by A. cantonensis infection.•Treatment with dexamethasone significantly reduced the expression of IDO, tryptophan and kynurenine. Angiostrongylus cantonensis is the major cause of eosinophilic meningitis worldwide. The imbalance of neurotoxic and neuroprotective metabolites in the kynurenine pathway (KP) have been suggested to contribute to the pathogenesis of central nervous system (CNS) infection. We hypothesized that KP may also be involved in parasitic eosinophilic meningitis. BALB/c mice were orally infected with 40 A. cantonensis L3, intraperitoneal dexamethasone at a dose of 500 µg/kg/day was administered from the seventh day of infection until the end of the study. The Evans blue method was used to analyze blood-brain barrier (BBB) dysfunction, and indoleamine 2,3-dioxygenase (IDO) proteins levels was measured by Western blot, immunohistochemistry (IHC), and immunofluorescence. Tryptophan and kynurenine concentrations were analyzed by IHC and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The concentrations of Evans blue, IDO, tryptophan and kynurenine in the different groups of mice were compared using the nonparametric Kruskal-Wallis test. BBB dysfunction was found in mice with eosinophilic meningitis. The administration of dexamethasone significantly decreased the amount of Evans blue. An increased IDO expression was shown in Western blot, IHC and immunofluorescence following 2–3 weeks infection. Increased tryptophan and kynurenine expressions in the brain and cerebrospinal fluid (CSF) were also found in IHC and LC-MS/MS studies. The administration of dexamethasone significantly decreased the amount of IDO, tryptophan and kynurenine. In conclusion, A. cantonensis infection inducing BBB damage, then increased the influx of tryptophan into CSF. The administration of dexamethasone significantly decreased the amount of IDO, tryptophan and kynurenine.