Ablation of CD11 c(hi) dendritic cells exacerbates Japanese encephalitis by regulating blood-brain barrier permeability and altering tight junction/adhesion molecules

作者：Kim Jin Hyoung; Hossain Ferdaus Mohd Altaf; Patil Ajit Mahadev; Choi Jin Young; Kim Seong Bum; Uyangaa Erdenebelig; Park Sang Youel; Lee John Hwa; Kim Bumseok; Kim Koanhoi; Eo Seong Kug^*

来源：Comparative Immunology, Microbiology and Infectious Diseases, 2016, 48: 22-32.

DOI：10.1016/j.cimid.2016.07.007

• CD11c(hi) DCs
• Japanese encephalitis virus
• Blood-brain barrier
• Tight junction
• Adhesion molecules

Japanese encephalitis (JE), characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV), is becoming a leading cause of viral encephalitis due to rapid changes in climate and demography. The blood-brain barrier (BBB) plays an important role in restricting neuroinvasion of peripheral leukocytes and virus, thereby regulating the progression of viral encephalitis. In this study, we explored the role of CD11 c(hi) dendritic cells (DCs) in regulating BBB integrity and JE progression using a conditional depletion model of CD11 c(hi) DCs. Transient ablation of CD11 c(hi) DCs resulted in markedly increased susceptibility to JE progression along with highly increased neuro-invasion of JEV. In addition, exacerbated JE progression in CD11chi DC-ablated hosts was closely associated with increased expression of proinflammatory cytokines (IFN-beta, IL-6, and TNF-alpha) and CC chemokines (CCL2, CCL3, CXCL2) in the brain. Moreover, our results revealed that the exacerbation of JE progression in CD11 c(hi) DC-ablated hosts was correlated with enhanced BBB permeability and reduced expression of tight junction and adhesion molecules (claudin-5, ZO-1, occluding, JAMS). Ultimately, our data conclude that the ablation of CD11 c(hi) DCs provided a subsidiary impact on BBB integrity and the expression of tight junction/adhesion molecules, thereby leading to exacerbated JE progression. These findings provide insight into the secondary role of CD11 c(hi) DCs in JE progression through regulation of BBB integrity and the expression of tight junction/adhesion molecules.

• 出版日期2016-10