Pathways underlying afferent signaling of bronchopulmonary immune activation to the central nervous system

Bronchopulmonary inflammation, such as that associated with asthma, activates afferent neural pathways. We recently demonstrated that localized inflammation in the lungs, induced by intratracheal administration of ovalbumin in ovalbumin-preimmunized mice (an animal model of asthma) results in activation of the dorsolateral part of the nucleus of the solitary tract, a major target of vagal afferent fibers innervating the lungs and airways. Activation of the nucleus of the solitary tract was evident in the absence of activation of the area postrema, a circumventricular organ, consistent with the hypothesis that localized inflammation in the bronchopulmonary system can signal to the central nervous system via specific neural pathways, in the absence of circulating proinflammatory mediators. The pattern of brain activation in ovalbumin-challenged mice differs from the pattern of activation in mice challenged with heat-killed Mycobacterium vaccae, suggesting that qualitative aspects of bronchopulmonary inflammation determine the overall pattern of brain activation. The mechanisms through which localized bronchopulmonary inflammation signals to the central nervous system is poorly understood, but appears to involve both vagal and spinal afferent pathways. In this chapter, we review our current understanding of the anatomical pathways through which localized inflammation in the bronchopulmonary system influences central nervous system function.