Abstract
During acute bacterial meningitis, recognition of the bacterial envelope by immune cells of the central nervous system (CNS) generates a robust response that is essential to clear bacteria. This response is further amplified during treatment when lytic antibiotics, required for cure, also generate a burst of highly inflammatory cell envelope debris. Different peptidoglycan (PG) subcomponents interact with neurons, glia, and the blood brain barrier resulting in the entire symptom complex of meningitis. Recently, this CNS-cell envelope signaling axis has been extended to non-inflammatory recognition of cell wall components circulating from endogenous bacteria to the brain resulting in both benefit and chronic damage. This review will describe the molecular details of a broad array of cell envelope-induced responses in the CNS and what current strategies can be implemented to improve clinical outcome.
Highlights
The bacterial cell envelope is one of the most powerful pathogen associated molecular patterns (PAMP) recognized by pattern recognition receptors (PRR) of the human immune system
In the central nervous system (CNS), detection of the cell envelope is critical to the course of bacterial meningitis, one of the most dreaded infectious diseases
Streptococcus pneumoniae, Neisseria meningitidis, and Hemophilus influenzae are the three classical pathogens associated with bacterial meningitis (McGill et al, 2016)
Summary
The bacterial cell envelope is one of the most powerful pathogen associated molecular patterns (PAMP) recognized by pattern recognition receptors (PRR) of the human immune system. Patients are treated with bacteriolytic antibiotics that are required for cure and cause the rapid release of highly reactive bacterial debris (Tuomanen et al, 1985a). These PG fragments and cell envelope polymers persist and continue to elicit the influx of leukocytes, brain edema, inflammatory cytokines, and neuronal death, causing further neurological damage. We will describe the molecular interactions between a broad array of cell envelope fragments with specific receptors in the CNS that contribute to a spectrum of responses from CNS homeostasis to acute or chronic inflammation
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