Poly I:C Induced Gene Expression Changes in Non-Human Primates IV

The respiratory epithelium is the body’s first line of defense to pathogens, pollutants, and other potentially injurious agents that can be inhaled. Sampling the upper respiratory tract is becoming a widely used technique in the clinic to examine the molecular changes in the diseased airway; however, it is unclear as to whether the responses in the upper respiratory tract (i.e. the nasal turbinates) reflect the changes that occur in the lower respiratory tract (i.e. trachea and lungs). Here, we assessed the responses to poly I:C, a synthetic double-stranded RNA molecule that is meant to mimic the acute effects of a viral infection, in both the upper and lower respiratory tracts of cynomolgus macaques. To do this, we compared the in vivo response after a nasal poly I:C challenge in a nasal scrape samples (performed using a nasal curette) to responses that occurred after ex vivo poly I:C stimulation in nasal scrapes, tracheal epithelial brushings, and lung tissue explants in non-human primates. Animals were sedated with ketamine (10-15 mg/kg) delivered i.m. For nasal scrapes, a nasal curette was used to take a sample from the nasal cavity (blind, but likely to be from the inferior/maxilloturbinate). After sedation, the left nasal cavity was sampled at T = 0. Saline or poly I:C (100 mg) was subsequently administered to the right nasal cavity using a Penn-Century microspray device. At T = 6h post-poly I:C administration animals were sedated once more and a nasal scrape was collected from the nasal turbinates in the right nasal cavity. For these studies, each treatment group had n = 12 non-human primates and within each treatment group there were n = 6 that were sensitized and n = 6 that were not sensitized to A.suum. 2 samples were removed as outliers (detected by PCA).