Peripheral neural detection of danger-associated and pathogen-associated molecular patterns

Area of Science:

• Neuroimmunology
• Cellular and Molecular Biology

Background:

• The nervous and immune systems exhibit bidirectional communication influencing inflammation.
• Cellular mechanisms for detecting danger-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) by the nervous system are not fully elucidated.

Purpose of the Study:

• To investigate whether the carotid body, a neural crest-derived tissue, can detect PAMPs and DAMPs through an inflammasome-dependent pathway, analogous to immune cells.

Main Methods:

• Primary human neutrophils and rat carotid body chemosensitive cells were stimulated with Toll-like receptor (TLR) agonists.
• Systemic inflammation was induced in C57Bl/6J mice using zymosan (a PAMP).
• Peripheral chemoafferent activity from isolated carotid body/carotid sinus nerve preparations and ventilation via whole-body plethysmography were measured.

Main Results:

• Carotid body glomus cells displayed immunoreactivity for TLR-2, TLR-4, NLRP1, and NLRP3 inflammasomes.
• Zymosan administration increased NLRP3 inflammasome and interleukin-1β expression in glomus cells.
• Systemic inflammation induced by zymosan led to a five-fold increase in carotid sinus nerve discharge and enhanced respiratory activity.

Conclusions:

• Activation of TLRs in carotid body chemosensitive glomus cells upregulates NLRP3 inflammasome expression and IL-1β production.
• IL-1β acts in an autocrine manner to augment peripheral chemoreceptor drive, linking innate immune sensing to neural output.