Sequential transmigration of polymorphonuclear cells and naive CD3+T lymphocytes across the blood-cerebrospinal-fluid barrier in vitro following infection with Echovirus 30.
Viral meningitis by non-polio enteroviruses (NPEV) is a major public health burden causing fatal outcomes especially in the younger population. Strong evidence exists that the blood-cerebrospinal-fluid (CSF) barrier (BCSFB) serves as an entry point for enterovirus and leucocytes into the central nervous system (CNS). Moreover, analysis of clinical CSF specimens of patients with a NPEV infection revealed a predominance of polymorphonuclear granulocytes (PMN) in the early phase and mononuclear cells in the later course of meningitis. By applying a functional in vitro model of the BCSFB consisting of human choroid plexus papilloma (HIBCPP) cells, we aimed to analyse the mechanisms of sequential migration of PMN and naive CD3+T lymphocytes following infection with Echovirus 30 (EV30). EV30 infection led to increased transmigration of PMN and naive CD3+T lymphocytes. Transmigration of PMN was significantly enhanced in the presence of naive CD3+T lymphocytes, but not vice versa. The barrier function was not differentially altered under the respective conditions. Infection with EV30 led to an upregulation of CXCL3 and CXCL11 on the RNA-level. Additional analysis of cytokine secretion revealed relatively high concentrations of IL-8, CCL20, CXCL3, CXCL10 and M-CSF. Overall, there was a predominantly polar direction of cytokine secretion to the basolateral side. IL-7 was the only cytokine which was strongly secreted to the apical side and that was enhanced following EV30 infection in our model. In conclusion, this study highlights the role of the choroid plexus and cytokines in regulating leucocyte entry into the CNS in the context of EV30 infection.
Paediatric Infectious Diseases, University Children's Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Tobias
T
Dahm
Paediatric Infectious Diseases, University Children's Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Franziska
F
Frank
Institute for Virology, University Hospital, Heinrich-Heine-University, Düsseldorf, Germany.
Ortwin
O
Adams
Department of Anaesthesiology and Surgical Intensive Care Medicine, University Medical Centre Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Holger A
HA
Lindner
Department of Anatomy, Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minatoku, Tokyo 105-8461, Japan.
Hiroshi
H
Ishikawa
Department of Statistics, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Christel
C
Weiss
Paediatric Infectious Diseases, University Children's Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Christian
C
Schwerk
Paediatric Infectious Diseases, University Children's Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Horst
H
Schroten
Paediatric Infectious Diseases, University Children's Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Tobias
T
Tenenbaum
Paediatric Infectious Diseases, University Children's Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. Electronic address: henriette.rudolph@medma.uni-heidelberg.de.
Henriette
H
Rudolph
D001812:Blood-Brain Barrier / Q000276:immunology* / Q000821:virology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology*; D054418:Chemokine CCL20 / Q000235:genetics / Q000276:immunology; D054357:Chemokine CXCL10 / Q000235:genetics / Q000276:immunology; D054371:Chemokine CXCL11 / Q000235:genetics / Q000276:immunology; D019743:Chemokines, CXC / Q000235:genetics / Q000276:immunology; D018920:Coculture Techniques; D029822:Enterovirus B, Human / Q000276:immunology* / Q000472:pathogenicity; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D015851:Interleukin-7 / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology; D008954:Models, Biological; D009504:Neutrophils / Q000276:immunology* / Q000821:virology; D020288:Papilloma, Choroid Plexus / Q000276:immunology / Q000473:pathology / Q000821:virology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology
C108355:CCL20 protein, human; C114753:CXCL10 protein, human; C515202:CXCL11 protein, human; C499707:CXCL3 protein, human; D054418:Chemokine CCL20; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D019743:Chemokines, CXC; C508605:IL7 protein, human; D015851:Interleukin-7; D016209:Interleukin-8; D016173:Macrophage Colony-Stimulating Factor
Blood-CSF barrier; Enterovirus; Inflammation; Leucocyte transmigration; Meningitis