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

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). Repeated sampling in NHPs sensitized (n = 4) and not sensitized (n =3) to Ascaris suum occurred at baseline (0h), 6h, 24h and 72h time points.