[29] Recognition of RSV though PRR is schematized in Fig. 1. Among the pro-inflammatory cytokines described below, IL-8 is a key molecule produced by epithelial cells and macrophages during the early response to hRSV and works as a chemoattractant in the recruitment of neutrophils, which infiltrate the site of infection.[35] Another important molecule of the innate response against hRSV infection C646 is

IL-1β, a pro-inflammatory cytokine involved in the antiviral response. First, hRSV stimulates PRR to induce the expression of pro-IL-1β (IL-1β precursor) and inflammasome components, trigged by TLR2/MyD88 that activates the NF-κB pathway.[33, 35] Second, the assembly of the inflammasome Cyclopamine concentration complex takes place and caspase-1 cleaves pro-IL-1β into IL-1β in response to the production of reactive oxygen species, cellular potassium efflux, or cathepsin leakage into the cytosol after lysosomal disintegration.[34,

36] The NF-κB pathway is important for the activation of an innate response against hRSV, not only for the cytokine response, but also for the formation of tight junctions between nasal epithelial cells.[37] Infection with hRSV induces the up-regulation of genes encoding structural components of tight junctions, including claudin-2, -4, -7, -9, -14, -19, occludin, ZO-2, cingulin and MAG-1, mediated by the protein kinase Cδ signalling.[37] This phenomenon seems to be beneficial for the replication of the virus, because inhibition of NF-κB and protein kinase Cδ

activation leads to an impairment of viral replication and formation of virus filaments.[37] In addition, the induction of tight junctions could increase the cell polarity necessary for viral budding.[13] Human RSV infection has been associated with an inefficient adaptive immune response, characterized by an excessive T helper type 2 (Th2) and a deficient IMP dehydrogenase antiviral Th1 response.[15, 36, 38] The Th1 responses usually involve the production of IFN-γ, IL-2 and tumour necrosis factor-α, whereas IL-4, IL-5, IL-10 and IL-13 secretion characterize Th2 responses. Further, a Th17 response has been associated with hRSV pathogenesis because it contributes to the development of asthma in infected children.[15, 39] Studies using an in vitro model comprising both human airway epithelial cells (A549 cells) and human immune cells (peripheral blood mononuclear cells) have shown that hRSV infection induces the production of IFN-γ,IL-4 and IL-17, suggesting that the three subsets (Th1, Th2 and Th17) can be activated upon viral infection.[40] Assays performed with peripheral blood mononuclear cells co-cultured with hRSV-infected A549 cells have also shown a Th2 and Th17 differentiation and the suppression of the generation of regulatory T cells.[8, 41] Indeed, as shown in Fig.