An important mucosal pathogen, and the most common cause of lower respiratory tract infections in children is respiratory syncytial virus (RSV). RSV is a negative-sense, single-stranded RNA virus of the family Paramyxoviridae. RSV enters the human body through the mucosa of the nasopharynx, where it infects epithelial cells in the presence of colonizing bacteria. GPCR & G Protein inhibitor Due to infection, the integrity of the epithelium is destroyed [[2, 3]]; consequently, RSV infections may result in enhanced translocation of bacterial ligands over the epithelium. Infection with RSV induces epithelial cells to

produce chemokines to attract innate immune cells to the site of infection [[4]]. During viral infection, resident and recruited innate immune cells detect viral infections, mainly by sensing viral nucleic acids. This

induces type I IFNs [[5]], the most important innate immune response against a viral infection [[6]]. Several pattern recognition receptors (PRRs) have been described CHIR 99021 to recognize specific components of RSV. The F-protein of RSV and RSV ssRNA are recognized by TLR4 [[7]] and TLR7 [[8]], respectively. RSV ssRNA has also been shown to be recognized by nucleotide-binding oligomerization domain-2 (NOD2) [[9]]. During infection, viral dsRNA is produced, which can be recognized by TLR3 [[10]], retinoic acid-inducible gene I (RIG-I) [[11]], and possibly also by melanoma differentiation-associated gene 5 (MDA-5), although the exact role of MDA-5 is still unclear [[12]]. The majority of RSV infections result in relatively

mild symptoms, comparable with those of a common cold. However, in some cases infection with RSV may result in a severe bronchio-litis. Previous studies have shown that the bacterial composition of the lower respiratory tract is Quisqualic acid not distinct from the upper respiratory tract, only that there are lower amounts of biomass [[13]]. Severe bronchiolitis is the result of an exaggerated proinflammatory response by RSV infected inflammatory cells [[14, 15]]. A massive influx of neutrophils in both the upper and lower airways [[4, 15, 16]] and airway obstruction can be the result. In particular, very young children are at increased risk of developing severe disease, which often leads to hospitalization. Due to the significant health burden of these infections, much effort has been invested into characterizing the risk factors contributing to disease severity. Age (<6 months), prematurity, and the presence of siblings have all been associated with increased severity [[17, 18]], though severe disease may still develop in otherwise healthy children. Hence, the pathogenesis of severe RSV disease is still poorly defined.