title: Ablation of CD11c(hi) dendritic cells exacerbates Japanese encephalitis by regulating blood-brain barrier permeability and altering tight junction/adhesion molecules.
abstract: 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 CD11c(hi) dendritic cells (DCs) in regulating BBB integrity and JE progression using a conditional depletion model of CD11c(hi) DCs. Transient ablation of CD11c(hi) DCs resulted in markedly increased susceptibility to JE progression along with highly increased neuro-invasion of JEV. In addition, exacerbated JE progression in CD11c(hi) DC-ablated hosts was closely associated with increased expression of proinflammatory cytokines (IFN-β, IL-6, and TNF-α) and CC chemokines (CCL2, CCL3, CXCL2) in the brain. Moreover, our results revealed that the exacerbation of JE progression in CD11c(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 CD11c(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 CD11c(hi) DCs in JE progression through regulation of BBB integrity and the expression of tight junction/adhesion molecules.
authors.affiliation: College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan 54596, Republic of Korea.
authors.forename: Jin Hyoung
authors.initials: JH
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan 54596, Republic of Korea.
authors.forename: Ferdaus Mohd Altaf
authors.initials: FM
authors.lastname: Hossain
authors.affiliation: College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan 54596, Republic of Korea.
authors.forename: Ajit Mahadev
authors.initials: AM
authors.lastname: Patil
authors.affiliation: College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan 54596, Republic of Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan 54596, Republic of Korea.
authors.forename: Seong Bum
authors.initials: SB
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan 54596, Republic of Korea.
authors.forename: Erdenebelig
authors.initials: E
authors.lastname: Uyangaa
authors.affiliation: College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan 54596, Republic of Korea; Department of Bioactive Material Sciences, Graduate School, Chonbuk National University, Jeonju 54896, Republic of Korea.
authors.forename: Sang-Youel
authors.initials: SY
authors.lastname: Park
authors.affiliation: College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan 54596, Republic of Korea; Department of Bioactive Material Sciences, Graduate School, Chonbuk National University, Jeonju 54896, Republic of Korea.
authors.forename: John-Hwa
authors.initials: JH
authors.lastname: Lee
authors.affiliation: College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan 54596, Republic of Korea.
authors.forename: Bumseok
authors.initials: B
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Pusan National University, School of Medicine, Yangsan 50612, Republic of Korea.
authors.forename: Koanhoi
authors.initials: K
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan 54596, Republic of Korea; Department of Bioactive Material Sciences, Graduate School, Chonbuk National University, Jeonju 54896, Republic of Korea. Electronic address: vetvirus@chonbuk.ac.kr.
authors.forename: Seong Kug
authors.initials: SK
authors.lastname: Eo
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000821:virology; D018845:CD11 Antigens / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology*; D004195:Disease Models, Animal; D004664:Encephalitis Virus, Japanese / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D004672:Encephalitis, Japanese / Q000503:physiopathology / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010539:Permeability; D062725:Tight Junction Proteins / Q000378:metabolism*; D019108:Tight Junctions / Q000821:virology; D019562:Viral Load
chemical_list: D018845:CD11 Antigens; D015815:Cell Adhesion Molecules; D016207:Cytokines; D062725:Tight Junction Proteins
keywords: Adhesion molecules; Blood-brain barrier; CD11c(hi) DCs; Japanese encephalitis virus; Tight junction