Time course change in expression of immune response markers of mouse brain infected with Angiostrongylus cantonensis

Autor: Yung-Yu Wang, 王永裕
Rok vydání: 2010
Druh dokumentu: 學位論文 ; thesis
Popis: 98
Angiostrongylus cantonensis is an important zoonotic parasite in Taiwan. When infective larvae are ingested by human, they enter the blood vessels of the intestinal tract and eventually reach the brain to develop into young adult worms and cause eosinophilic meningoencephalitis. Other mammals like mouse and rabbits serve as animal models for human angiostrongyliasis. Previous studies revealed that cerebrospinal fluid contained high level Th2 cytokines like IL-4 and IL-5 in infected mice. We also observed the expression of Th2-type cytokines in mouse parenchyma at 14 days postinfection (dpi). In this study, we used RT-PCR, H&E stain and immunohistochemistry techniques to monitor the time-course change in cytokines in the brain, to understand the change in immune response in the brain of infected mouse. ICR mice were each orally infected with 30 infective larvae and sacrificed at 10,11,12,13 and 14 dpi. Section of the brains revealed that spotted hemorrhage appeared in the mouse brain at 9-10 dpi, possibly related to migration of the worms. Leukocytes infiltration into the third ventricle was more drastic thanthat of the meninge at 13 dpi. The gene expression of TNF-α, IL-1β and the Th1 cytokine-IFN-γ started to elevate at 10 dpi. TNF-α and IL-1β expression reached their peak on 13 dpi. IFN-γ expression increased slightly on 11 dpi and peaked 12-13 dpi. IL-5 expression increased significantly during 11 to 14 dpi. No apparent change in expression of NGF and NT-3 were observed. BDNF expression, however, increased significantly between 10-14 dpi except at 13 dpi which was almost normal. Proinflammatory cytokines may affect the permeability in the brain and resulted in leukocyte infiltration. The brain might be able to postpone inflammatory response after hemorrhage occurred in the brain, hence cellular infiltration occurred a few days afterward. Neurotrophic factors and Th2 cytokines are known to help neuron survival. Neurotrophic factor might have the effect of retarding inflammatory response in early eosinophilic meningoencephalitis cause by Angiostrongylus cantonensis infection in mice. Thus, although inflammation response kept on expanding, neuronal cells could secrete neurotrophic factors and Th2 cytokines to sustain their life in the presence of inflammatory response.
Databáze: Networked Digital Library of Theses & Dissertations