The Early Adaptive Immune Response in the Pathophysiological Process of Pneumococcal Meningitis.
BACKGROUND
The adaptive immune system has been considered to play a minimal role in the early host response during bacterial meningitis.


METHODS
We investigated the progression and outcome of pneumococcal meningitis in Rag1-/-mice lacking functional B and T cells by assessing overall and symptom-free survival, bacteriological and histological studies, as well as flow cytometry and measurements of proinflammatory mediators.


RESULTS
The intracerebral injection of S. pneumoniae D39 induced the recruitment of B and T cells (CD4+, γδ and natural killer) into the brain of wild-type mice. Mice with no functional B and T cells developed clinical symptoms and succumbed to the infection earlier than the wild-type group. In the CNS, Rag1-/-mice showed lower levels of interleukin 1β, reduced microglial proliferation, and impaired granulocyte recruitment with an earlier spread of pneumococci into the bloodstream, compared with wild-type mice. Lack of B and T cells resulted in a severe impairment of bacterial clearance in blood, spleen, and liver and an exaggerated systemic inflammatory response.


CONCLUSIONS
B and T cells are important effector cells delaying the spread of pneumococci from the brain to the systemic circulation and shaping the immune response, thereby prolonging the survival of the host in the absence of antibiotic treatment.
Institute of Neuropathology, University Medical Center Göttingen, Georg-August University.
Sandra
S
Ribes
Institute of Neuropathology, University Medical Center Göttingen, Georg-August University.
Stefan
S
Nessler
Institute of Neuropathology, University Medical Center Göttingen, Georg-August University.
Ev-Christin
EC
Heide
Department of Genetic Epidemiology, University Medical Center Göttingen, Georg-August University.
Dörthe
D
Malzahn
Institute of Pathology, University Medical Center Göttingen, Georg-August University.
Christina
C
Perske
Institute of Neuropathology, University Medical Center Göttingen, Georg-August University.
Wolfgang
W
Brück
Institute of Neuropathology, University Medical Center Göttingen, Georg-August University.|Department of Geriatrics, Evangelisches Krankenhaus Göttingen-Weende, Germany.
Roland
R
Nau
D056704:Adaptive Immunity; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001921:Brain / Q000276:immunology* / Q000382:microbiology / Q000648:ultrastructure; D016207:Cytokines / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000276:immunology; D007694:Killer Cells, Natural; D008586:Meningitis, Pneumococcal / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology; D013154:Spleen / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D053583:Interleukin-1beta
B cell; CD4+ T cell; IL-1β; S. pneumoniae; granulocyte; inflammatory response; meningitis; microglia; natural killer T (NKT) cell; γδ T cell