title: CXCL16 contributes to neutrophil recruitment to cerebrospinal fluid in pneumococcal meningitis.
abstract: In this study, we analyzed the expression and function of CXCL16 in pneumococcal meningitis. CXCL16 was found to be up&#x2010;regulated in RAW264.7 macrophages (but not in neutrophils and endothelial cells) upon pneumococcal stimulation, in the cerebrospinal fluid of patients, and in the brains as well as the cerebrospinal fluid of mice with pneumococcal meningitis. CXCL16 up&#x2010;regulation in vivo was dependent on Toll&#x2010;like receptor (TLR) 2/TLR4 and MyD88 signaling. Neutralization of CXCL16 in animals before intracisternal pneumococcal infection (using anti&#x2010;CXCL16 antibodies) resulted in reduced cerebrospinal fluid pleocytosis. In vitro, murine neutrophils expressed the CXCL16 receptor CXCR6 and showed dose&#x2010;dependant migration toward a CXCL16 gradient. Thus, this study implicates CXCL16 as an additional neutrophil chemoattractant in cerebrospinal fluid in early pneumococcal meningitis.
authors.affiliation: Department of Neurology, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany. Bianca.Woehrl@med.uni-muenchen.de
authors.forename: Bianca
authors.initials: B
authors.lastname: Woehrl
authors.forename: Matthias
authors.initials: M
authors.lastname: Klein
authors.forename: Tobias  A
authors.initials: T
authors.lastname: Rupprecht
authors.forename: Helga
authors.initials: H
authors.lastname: Schmetzer
authors.forename: Barbara
authors.initials: B
authors.lastname: Angele
authors.forename: Hans
authors.initials: H
authors.lastname: Häcker
authors.forename: Georg
authors.initials: G
authors.lastname: Häcker
authors.forename: Hans-Walter
authors.initials: HW
authors.lastname: Pfister
authors.forename: Uwe
authors.initials: U
authors.lastname: Koedel
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000276:immunology; D002460:Cell Line; D002555:Cerebrospinal Fluid / Q000166:cytology* / Q000276:immunology; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology; D020869:Gene Expression Profiling; D006801:Humans; D008264:Macrophages / Q000276:immunology; D008586:Meningitis, Pneumococcal / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology*; D054387:Receptors, CXCR / Q000276:immunology; D000075744:Receptors, CXCR6; D051195:Toll-Like Receptor 2 / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology
chemical_list: D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; C498926:Cxcl16 protein, mouse; C482906:Cxcr6 protein, mouse; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D054387:Receptors, CXCR; D000075744:Receptors, CXCR6; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4