Primary Peripheral Human Plasmacytoid Dendritic Cell Responses to Rotavirus Infection: Mechanisms of Induction and Consequences for Pathogenesis

• Main Author: Deal, Emily M
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2010
• Subjects: Immunology; Microbiology; Virology
• ISBN: 9798664721638

Rotaviruses are the leading cause of severe dehydrating diarrhea in children worldwide. Rotavirus-induced immune responses, especially the T and B cell responses, have been extensively characterized; however, little is known about innate immune mechanisms involved in the control of rotavirus infection. Although increased levels of systemic type I interferon correlate with accelerated resolution of rotavirus disease, multiple rotavirus strains, including rhesus rotavirus (RRV), have been demonstrated to antagonize type I interferon production in a variety of epithelial and fibroblast cell types through several mechanisms, including degradation of multiple interferon regulatory factors by a viral nonstructural protein. Dendritic cells (DCs), a highly specialized subset of professional antigen- presenting cells, play a central role in the initiation of innate and adaptive immunity. Plasmacytoid DCs (pDCs), which secrete the type I interferons, as well as a variety of other cytokines and chemokines, have been documented to have multiple antiviral effects. These studies characterize the primary human pDC response to rotavirus, while elucidating the viral and cellular requirements for this response. Additionally, these studies demonstrate that type I interferon derived from primary pDCs is necessary and sufficient for B cell activation by rotavirus.