The Coates Laboratory explores differences in the inflammatory response to viral respiratory infections in children and adults. Although young children and elderly adults bear a disproportionate burden of morbidity and mortality associated with viral respiratory infections, little is known about the mechanisms placing these populations at increased risk. The Coates Laboratory is currently investigating the role of innate immune responses in severity of illness in influenza and respiratory syncytial virus infections. Elucidation of the mechanisms underlying age-related susceptibility and resistance to disease may contribute to the broader understanding of innate immunity and its role in critical illness.
Respiratory Syncytial Virus
Severe Acute Respiratory Syndrome Coronavirus 2
Bria Coates, MD
PATHOPHYSIOLOGY OF INFLUENZA A VIRUS-INDUCED LUNG INJURY IN JUVENILES
Recent clinical data thwart the long-standing dogma that children with influenza have increased morbidity and mortality due to impaired viral clearance. Preliminary data from Dr. Coates and her research team identify an altered innate immune response in IAV-infected juvenile mice as a critical parameter in disease progression. Specifically, they show that increased lung injury in IAV-infected juvenile mice is associated with robust activation of the NOD-like receptor (NLR) protein NLRP3, resulting in increased IFNa/b and IL-1b/18 levels that persist beyond viral elimination. In addition, juvenile lungs produce more MCP-1 and recruit more inflammatory monocytes during IAV infection, which perpetuates NLRP3 activation. Dr. Coates and her research team observe that juvenile recruited monocytes are uniquely inflammatory, and prevention of their recruitment during IAV infection protects juvenile mice from IAV-mediated lung injury. They hypothesize that age-specific, cell autonomous differences in the innate immune response to IAV contribute to the robust and sustained activation of the NLRP3 inflammasome and exacerbate IAV-induced lung injury in juvenile mice.
NASAL EPITHELIAL GENE EXPRESSION AND SUSCEPTIBILITY TO VIRAL PNEUMONIA IN CHILDREN
Viral pneumonia is a leading cause of hospitalization in children less than 5 years of age. While influenza virus and respiratory syncytial virus frequently cause viral pneumonia in young children, the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), only rarely causes viral pneumonia in children. Why young children are so much more likely to develop severe influenza virus and respiratory syncytial virus infections, and so much less likely to develop severe SARS-CoV-2 infections, is unknown. Analysis of transcriptional profiles in nasal samples obtained by nearly painless curettage can reveal important information about the host response to viral infections. The nasal epithelium is the first line of defense against viral respiratory infections and may dictate downstream inflammatory and antiviral responses. In children with respiratory syncytial virus infection, Dr. Coates and her research team found a transcriptional signature in nasal samples at the time of admission that was associated with infection outcomes, including duration of oxygen dependence and intensive care unit stay. Therefore, analysis of the host response to influenza virus, respiratory syncytial virus, and SARS-CoV-2 in nasal samples may reveal alterations in gene expression that determine resilience and susceptibility to viral pneumonia.