DENDRITIC CELLS, RSV AND INFLUENZA INFECTION IN CHILDREN

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DESCRIPTION (provided by applicant): Respiratory syncytial virus (RSV) is the principal etiologic agent of bronchiolitis and viral pneumonia in infants and young children worldwide. Influenza viruses also contribute to significant number of hospitalizations among children. While the clinical manifestations are similar, there are remarkable differences in terms of their immune responses. In a simplified comparison, RSV does not induce protective immunity, there is no available vaccine, and it is associated with recurrent wheezing. In contrast, influenza does induce a more effective protective immune response, vaccines are quite effective, and it is not associated with long-term wheezing. This provides an ideal setting for a comparative analysis of the immune responses of children with these two viral infections. Dendritic cells (DCs) constitute a complex system of cells with a unique ability to induce primary immune responses. In addition, emerging evidence indicates that DCs control cytokine production by T cells and regulate the Th1/Th2 balance of the immune responses. Numerous studies have demonstrated the importance of the interaction between viruses and different DCs subsets and how that initial interaction influences the development of the subsequent immune responses. Although to date, not much is known about the interaction between DCs and RSV, our preliminary results suggest a direct participation of DCs in the immune response to RSV infection in children. Our hypothesis is that RSV and influenza virus target DC differentially leading to different immune responses, mostly deleterious in case of RSV and protective in case of influenza. We will begin to address this hypothesis in the following specific aims: 1. To determine how RSV and influenza infection affect human DC subsets in vivo, and 2. To determine how RSV and influenza infection affect human DC subsets in vitro, These studies will permit us to define the nature of the DC subset(s) that constitute the target of RSV and influenza infection in children, and begin to identify the mechanisms implicated in the interaction between these respiratory viruses and DCs.