Experimental pneumococcal meningitis in mice: a model of intranasal infection.
Effective laboratory animal models of bacterial meningitis are needed to unravel the pathophysiology of this disease. Previous models have failed to simulate human meningitis by using a directly intracerebral route of infection. Hyaluronidase is a virulence factor of Streptococcus pneumoniae. In this study, a novel model of murine meningitis is described. Intranasal administration of S. pneumoniae with hyaluronidase induced meningitis in 50% of inoculated mice, as defined by a positive cerebrospinal fluid (CSF) culture and an inflammatory infiltrate in the meninges. None of the mice inoculated without hyaluronidase developed meningitis. Hyaluronidase was found to facilitate pneumococcal invasion of the bloodstream after colonization of the upper respiratory tract. Meningitis was characterized by pleocytosis of CSF and the induction of proinflammatory cytokines and CXC chemokines in brain tissue. These results indicate that this murine model mimics important features of human disease and allow for the use of this model for studying issues related to the pathophysiology and the treatment of pneumococcal meningitis.
Department of Pediatrics, University Hospital Vrije Universiteit, and Department of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands. p.j.zwijnenburg@amc.uva.nl
P J
PJ
Zwijnenburg
T
T
van der Poll
S
S
Florquin
S J
SJ
van Deventer
J J
JJ
Roord
A M
AM
van Furth
D000818:Animals; D016470:Bacteremia / Q000382:microbiology; D001921:Brain / Q000276:immunology; D019743:Chemokines, CXC / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006821:Hyaluronoglucosaminidase / Q000494:pharmacology; D007964:Leukocytosis / Q000134:cerebrospinal fluid; D008578:Meninges / Q000473:pathology; D016920:Meningitis, Bacterial / Q000134:cerebrospinal fluid / Q000382:microbiology*; D051379:Mice; D011008:Pneumococcal Infections / Q000134:cerebrospinal fluid / Q000382:microbiology*; D012220:Rhinitis / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000472:pathogenicity; D014774:Virulence
D019743:Chemokines, CXC; D016207:Cytokines; D006821:Hyaluronoglucosaminidase