Project description:Air-liquid interface cultures are extensively used to model chronic respiratory diseases. Comparative transcriptomics between cultured cells and fresh nasal brushings from patients suggests a high degree of correlation.
Project description:This study aims to explore the relationship between the respiratory virome, specifically bacteriophages, HERV and the host response in ARDS and to assess their value in predicting the prognosis of ARDS.
Project description:Viral respiratory infections significantly affect young children, particularly extremely premature infants, resulting in high hospitalization rates and increased health-care burdens. Despite posing substantial health risks, airway immune responses in early life remain largely unexplored. Nasal epithelial cells, the primary defense against respiratory infections, are vital for understanding nasal immune responses and serve as a promising target for uncovering underlying molecular and cellular mechanisms. Using a trans-well pseudostratified nasal epithelial cell system, we examined age-dependent developmental differences and antiviral responses to influenza A and respiratory syncytial virus through systems biology approaches. Our studies revealed differences in innate-receptor repertoires, distinct developmental pathways, and differentially connected antiviral network circuits between neonatal and adult nasal epithelial cells. Consensus network analysis identified unique and shared cellular networks for influenza A and respiratory syncytial virus, emphasizing highly relevant virus-specific pathways. This research highlights the importance of nasal epithelial cells in innate antiviral immune responses and offers novel insights that should enable a deeper understanding of age-related differences in nasal epithelial cell immunity following respiratory virus infections.
Project description:Exposure to cigarette smoke (CS) is etiologically linked to the development of fatal respiratory diseases, and there is a need to understand the mechanisms whereby CS causes damage. While animal models have provided valuable insights into smoking-related respiratory tract damage, modern toxicity testing calls for reliable in vitro models as alternatives for animal experimentation. Primary cells and immortalized cell lines can be used to gain some insight; however, the three-dimensional organotypic culture systems probably better mimic the morphological, physiological, and molecular attributes of the human respiratory tract. Even though the bronchus, bronchioles, and lung parenchyma are the primary sites of smoking-related respiratory disease manifestation, the nasal epithelium has been proposed as a surrogate tissue to study the effects of smoking on the respiratory tract. Here, we report on a repeated whole mainstream CS exposure of nasal and bronchial organotypic tissue cultures from which transcriptomic data were collected at several post-exposure time points. Despite the remarkably similar histology and cellular response to whole CS in both tissue types, as measured by cellular staining and cytokine secretion assessment, transcriptomic analyses combined with quantitative biological network modeling identified biological mechanisms that were unique to bronchial tissue at late post-exposure time points. Organotypic models therefore appear to be a promising alternative to animal experimentation, and provide species-relevant insights into the effects of CS exposure on the respiratory system.
Project description: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.