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Published on: January 17, 2014
The Early Adaptive Immune Response in the Pathophysiological Process of Pneumococcal Meningitis
Sandra Ribes1, Stefan Nessler1, Ev-Christin Heide1
1Institute of Neuropathology, University Medical Center Göttingen, Georg-August University.
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.
Insights
Adaptive immunity, involving B and T cells, is crucial in bacterial meningitis. These cells delay pathogen spread and prolong host survival by modulating the immune response, even without antibiotics.
Area of Science:
- Immunology
- Neuroscience
- Infectious Diseases
Background:
- The adaptive immune system's role in early bacterial meningitis is traditionally considered minimal.
- Pneumococcal meningitis is a severe infection with significant host response challenges.
Purpose of the Study:
- To investigate the role of B and T cells in pneumococcal meningitis progression and outcome.
- To elucidate the impact of adaptive immunity on host survival and pathogen clearance.
Main Methods:
- Utilized Rag1-/- mice lacking B and T cells to study pneumococcal meningitis.
- Assessed survival, bacteriology, histology, flow cytometry, and inflammatory mediators.
Main Results:
- Mice lacking B and T cells showed earlier mortality and exacerbated clinical symptoms.
- Absence of B and T cells led to impaired bacterial clearance, reduced inflammatory mediators in the CNS, and increased pathogen spread to systemic circulation.
Conclusions:
- B and T cells are vital effector cells in bacterial meningitis.
- These cells delay pneumococcal spread from the brain and shape the immune response, enhancing host survival.
- Findings highlight the importance of adaptive immunity in managing meningitis, independent of antibiotic treatment.
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