Bacterial Meningitis

Bacterial Meningitis: Study Finds Neuroimmune Axis That Exacerbates Host Defenses

Bacterial meningitis is a life-threatening infection that affects more than 2.5 million people annually, according to recent studies. Recently, researchers discovered that Nav1.8+ nociceptors signal immune cells in the meninges via the neuropeptide calcitonin gene-related peptide (CGRP) during infection; this neuroimmune axis suppresses host defenses further increasing the risk of bacterial meningitis.

Bacterial Meningitis: Study Finds Neuroimmune Axis That Exacerbates Host Defenses
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According to a study published in Nature, bacterial meningitis causes pain and headaches by activating nociceptive sensory neurons within the meninges that then signal immune cells via CGRP. This suppresses macrophage chemokine expression, neutrophil recruitment, as well as dural antimicrobial defences – thus allowing brain invasion.

To test their hypothesis, the researchers abated nociceptor neurons in meninges to reduce meningeal and brain invasion by two bacterial pathogens: Streptococcus pneumoniae and Streptococcus agalactiae. They discovered that S. pneumoniae activated nociceptors through its pore-forming toxin pneumolysin, leading to the release of CGRP from nerve terminals.

The team then demonstrated that CGRP interacted with receptor activity modifying protein 1 (RAMP1) on meningeal macrophages to polarize their transcriptional responses, impairing host defenses and exacerbating bacterial meningitis. Conversely, macrophage-specific RAMP1 deficiency or pharmacological blockade of RAMP1 enhanced immune responses as well as bacterial clearance from both meninges and brain.

The study’s results are significant because they offer new insight into how bacteria use CGRP-RAMP1 signaling in meningeal macrophages to facilitate brain invasion. By targeting this neuroimmune axis within meninges, researchers may be able to strengthen host defences and develop treatments for bacterial meningitis.

This neuroimmune axis weakens host defenses and makes bacterial meningitis worse. A study demonstrated that ablation of nociceptor neurons reduced meningeal and brain invasion by two bacterial pathogens: Streptococcus pneumoniae and Streptococcus agalactiae.

S. pneumoniae in particular activated nociceptors through its pore-forming toxin pneumolysin, releasing CGRP from nerve terminals. CGRP then worked through receptor activity-modifying protein 1 (RAMP1) on meningeal macrophages to polarize their transcriptional responses, suppressing macrophage chemokine expression, neutrophil recruitment, and dural antimicrobial defenses.

The study’s results indicate bacteria hijack CGRP-RAMP1 signaling in meningeal macrophages to facilitate brain invasion. Targeting this neuroimmune axis within the meninges could boost host defenses and potentially lead to treatments for bacterial meningitis.

Researchers believe their discoveries could have important ramifications for the development of treatments for bacterial meningitis, which remains a serious public health problem. By targeting the neuroimmune axis in meninges, researchers hope to strengthen host defenses against bacterial invasion and improve outcomes for those suffering from this devastating infection.

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