Research Article: Increased 14-3-3β and γ protein isoform expressions in parasitic eosinophilic meningitis caused by Angiostrongylus cantonensis infection in mice

Date Published: March 7, 2019

Publisher: Public Library of Science

Author(s): Hung-Chin Tsai, Yu-Hsin Chen, Chuan-Min Yen, Susan Shin-Jung Lee, Yao-Shen Chen, Ritu Chakravarti.


The 14-3-3 proteins are cerebrospinal fluid (CSF) markers of neuronal damage during infectious meningitis and Creutzfeldt-Jakob disease. Little is known about dynamic changes in the individual isoforms in response to parasitic eosinophilic meningitis. The purposes of this study were to determine the 14-3-3 protein isoform patterns, examine the kinetics and correlate the severity of blood brain barrier (BBB) damage with the expressions of these markers in mice with eosinophilic meningitis.

Partial Text

Angiostrongylus cantonensis, also known as rat lungworm, is the main etiology of human eosinophilic meningitis or meningoencephalitis in southeast Asia and the Pacific region [1–5]. Humans are infected with A. cantonensis by ingesting freshwater and terrestrial snails and slugs [5–8]. The major intermediate hosts for A. cantonensis in Taiwan are the African giant snail (Achutina fulica) and golden apple snail (Ampullarium canaliculatus) [4, 7–8]. When infection occurs in non-permissive hosts such as humans and mice, the development of the parasites will stop at the young-adult worm stage, causing brain damage and inducing eosinophilia in the blood and cerebral spinal fluid (CSF) [8–10]. In addition, brain apoptosis [11], the presence of 14-3-3 β protein [12] and dysfunction of the blood brain barrier (BBB) with CSF eosinophilia have been reported in mice and humans infected with A. cantonensis [8–10, 13].

In this study, we found significant increases in CSF 14-3-3 protein isoforms β and γ in the second and third weeks after infection compared to the controls and those infected for 1 week, which was consistent with the severity of BBB damage as assessed using the Evans blue assay, hematoxylin and eosin staining and increased expressions of tight junctional proteins occludin and claudin-5 in Western blot analysis and IHC studies. Using IHC to assess the distribution of 14-3-3 protein isoforms in the mice brain meninges, we also found that the expressions of 14-3-3 protein isoforms β, γ, ε and τ/θ in the brain meninges increased over a 3-week period after infection.

The results of the current study suggest that the mice with eosinophilic meningitis with increased expressions of 14-3-3 protein isoforms β and γ in the CSF and brain meninges tended to have more severe dysfunction of the BBB as evidenced by Evans blue staining, brain hematoxylin and eosin staining, and changes in the expressions of the tight junctional proteins occludin and claudin-5. These results shed light on the role of 14-3-3 proteins in eosinophilic meningitis caused by A. cantonensis.




Leave a Reply

Your email address will not be published.