Immunomodulatory effects of sensory nerves during respiratory syncytial virus infection in rats

Abstract

Respiratory syncytial virus (RSV) infection is associated with exaggerated neurogenic inflammation in the airways. This study sought to determine whether irritation of the mucosal sensory fibers affects the recruitment of lymphocytes and monocytes to RSV-infected airways. Pathogen-free rats were inoculated with RSV or with virus-free medium and were injected 5 days later with capsaicin to stimulate airway sensory nerves. Bronchoalveolar lavage was performed 1, 5, or 10 days after nerve stimulation, and samples were analyzed by differential cell count and flow cytometry. Without nerve stimulation, RSV caused a minimal increase in the number of lymphocytes and monocytes above pathogen-free control levels. After nerve stimulation, numerous lymphocytes, predominantly CD4+ T cells, and monocytes were recruited in the airways of infected rats, whereas no difference was found in pathogen-free controls. RSV induced overexpression of the neurokinin 1 (NK1) receptor for substance P on discrete lymphocyte subpopulations within the bronchial-associated lymphoid tissue (BALT), and treatment with a specific NK1 receptor antagonist abolished the recruitment of both lymphocytes and monocytes to infected airways. Our data suggest that airborne irritants stimulating mucosal sensory fibers during RSV infection exert important immunomodulatory effects by attracting to the infected airways selected lymphocyte subpopulations from the local BALT as well as monocytes.

Neural-endocrine mechanisms of respiratory syncytial virus-associated asthma in a rat model

“…RSV suspensions were prepared using a previously described method Auais et al, 2003). Confluent monolayers of HeLa cells were infected with RSV strain A2, and the infection was allowed to progress at 37°C in 5% CO 2 atmosphere until 100% of the cells exhibited a cytopathic effect (for 2-5 days).…”

Pulmonary C Fibers Modulate MMP-12 Production via PAR2 and Are Involved in the Long-Term Airway Inflammation and Airway Hyperresponsiveness Induced by Respiratory Syncytial Virus Infection

“…Pulmonary C fibers (PCFs) are activated by various exogenous chemical substances and endogenous ligands and result in cough, dyspnea, mucus secretion, and bronchoconstriction (7,8). Capsaicin-stimulating mucosal sensory fibers during the acute stage after RSV infection exerted important immunomodulatory effects by attracting selected lymphocyte subpopulations from the local bronchiolar lavage fluid (BALF), as well as monocytes, to the infected airways (9). Substance P (SP)-immunoreactive fibers increased during persistent RSV infection (10), indicating that persistent RSV infection induces persistent innervating fiber activation in the airways.…”

Neurotrophins and Tonsillar Hypertrophy in Children With Obstructive Sleep Apnea

“…Indeed, anti-NGF antibody inhibited NK1 receptor up-regulation and neurogenic inflammation in RSV-infected lungs (15). Similarly, a specific NK1 receptor antagonist abolished the recruitment of both lymphocytes and monocytes to infected airways thereby reducing the local inflammatory response (14). Recently a study done in rats showed that administration of palivizumab 24 h before virus inoculation prevented the development of abnormal neurogenic inflammatory responses (22).…”

“…It has now been recognized by several epidemiologic studies that factors such as environmental smoking, allergies, and intercurrent respiratory infections are all associated with either transient or persistent hypertrophy of lymphadenoid tissue in the upper airways of snoring children (10 -12). Interestingly, all of these risk factors involve the generation of an inflammatory response, suggesting that the latter may promote the onset and maintenance of proliferative signals to lymphadenoid tissues.Bronchial-associated lymphoid tissue in the lungs of RSVinfected rats express high levels of the neurokinin 1 (NK1) receptor for substance P that is released from subepithelial sensory nerve fibers, a part of the nonadrenergic noncholinergic system (13,14). Furthermore, nerve growth factor (NGF), a major controller of sensorineural development and immuno-inflammatory responses, and its tyrosine kinase A receptor (trkA) are both overexpressed in rat lungs after respiratory syncytial virus (RSV) inoculation (15).…”

“…Bronchial-associated lymphoid tissue in the lungs of RSVinfected rats express high levels of the neurokinin 1 (NK1) receptor for substance P that is released from subepithelial sensory nerve fibers, a part of the nonadrenergic noncholinergic system (13,14). Furthermore, nerve growth factor (NGF), a major controller of sensorineural development and immuno-inflammatory responses, and its tyrosine kinase A receptor (trkA) are both overexpressed in rat lungs after respiratory syncytial virus (RSV) inoculation (15).…”