CXCL16 contributes to neutrophil recruitment to cerebrospinal fluid in pneumococcal meningitis.
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.
Woehrl
Bianca
B
Department of Neurology, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany. Bianca.Woehrl@med.uni-muenchen.de
Klein
Matthias
M
Rupprecht
Tobias  A
T
Schmetzer
Helga
H
Angele
Barbara
B
Häcker
Hans
H
Häcker
Georg
G
Pfister
Hans-Walter
HW
Koedel
Uwe
U
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
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