Insufficiency in airway interferon activation defines clinical severity to infant RSV infection

Chin-Yi Chu; Xing Qiu; Matthew N. McCall; Lu Wang; Anthony Corbett; Jeanne Holden-Wiltse; Christopher Slaunwhite; Qian Wang; Christopher Anderson; Alex Grier; Steven R. Gill; Gloria S. Pryhuber; Ann R. Falsey; David J. Topham; Mary T. Caserta; Edward E. Walsh; Thomas J Mariani

We were interested in understanding the role of the airway microbiota in defining clinical responses to RSV in infants. We failed to find a strong association between the presence/absence of microbial pathogens and severity. However, we confirmed a report published during our studies indicating a higher burden of H. influenzae in infants with severe clinical symptoms requiring hospitalization (Fig. 2) . Although other taxa were associated with airway gene expression, we were somewhat surprised to find no other OTUs were significantly associated with severity. It is worth knowing, 16S ribosomal RNA sequencing was not able to identify S. pneumoniae at the species level. Given our prior studies revealing a large impact of the microbiota upon gene expression in the airway, we studied the inter-relationships between the airway microbiome, airway gene expression and clinical severity. In general, these analyses confirmed that the existence of known pathogens, particularly bacteria, are strongly associated with gene expression in asymptomatic 35, 47 and symptomatic 47 infants. We considered the specific effect of the microbiota/H. flu on the relationship between gene expression and RSV severity. The results are consistent with H. flu altering the nature of the inflammatory response, from myeloid-predominant to CD4/8 T lymphocyte-predominant. These data provide a currently untested hypothesis for a potential mechanism whereby H. influenzae contributes to severe responses at the molecular and cellular level, which is a focus of current investigation.