Leukocyte attraction by CCL20 and its receptor CCR6 in humans and mice with pneumococcal meningitis.
We previously identified CCL20 as an early chemokine in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis but its functional relevance was unknown. Here we studied the role of CCL20 and its receptor CCR6 in pneumococcal meningitis. In a prospective nationwide study, CCL20 levels were significantly elevated in the CSF of patients with pneumococcal meningitis and correlated with CSF leukocyte counts. CCR6-deficient mice with pneumococcal meningitis and WT mice with pneumococcal meningitis treated with anti-CCL20 antibodies both had reduced CSF white blood cell counts. The reduction in CSF pleocytosis was also accompanied by an increase in brain bacterial titers. Additional in vitro experiments showed direct chemoattractant activity of CCL20 for granulocytes. In summary, our results identify the CCL20-CCR6 axis as an essential component of the innate immune defense against pneumococcal meningitis, controlling granulocyte recruitment.
Department of Neurology, Ludwig-Maximilians-University, Munich, Germany.
Matthias
M
Klein
Department of Neurology, University of Amsterdam, Amsterdam, The Netherlands; Center of Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
Matthijs C
MC
Brouwer
Department of Neurology, Ludwig-Maximilians-University, Munich, Germany.
Barbara
B
Angele
Department of Neurology, University of Amsterdam, Amsterdam, The Netherlands; Center of Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
Madelijn
M
Geldhoff
Genetrix, Madrid, Spain.
Gabriel
G
Marquez
Departamento de Immunologia y Oncologia, Centro National de Biotecnologia, Madrid, Spain.
Rosa
R
Varona
Institute for Medical Microbiology and Hygiene, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
Georg
G
Häcker
Medical Department III, Ludwig-Maximilians-University, Munich, Germany.
Helga
H
Schmetzer
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
Hans
H
Häcker
Department Genetics of Microorganisms, University of Greifswald, Greifswald, Germany.
Sven
S
Hammerschmidt
Center of Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands; Department of Medical Microbiology, University of Amsterdam, Amsterdam, The Netherlands.
Arie
A
van der Ende
Department of Neurology, Ludwig-Maximilians-University, Munich, Germany.
Hans-Walter
HW
Pfister
Department of Neurology, University of Amsterdam, Amsterdam, The Netherlands; Center of Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
Diederik
D
van de Beek
Department of Neurology, Ludwig-Maximilians-University, Munich, Germany.
Uwe
U
Koedel
D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015153:Blotting, Western; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D016022:Case-Control Studies; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008586:Meningitis, Pneumococcal / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011379:Prognosis; D011446:Prospective Studies; D054399:Receptors, CCR6 / Q000502:physiology*; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D054418:Chemokine CCL20; D054399:Receptors, CCR6