Plasmacytoid dendritic cells (pDCs) are important in innate and adaptive immune responses against viral infections, producing remarkable levels of type I interferon as well as other immunomodulatory cytokines. In vitro, pDCs can control replication of human immunodeficiency virus (HIV). Following natural challenge with simian immunodeficiency virus (SIV), PDCs infiltrate the vaginal mucosa. Despite this, pDCs are unable to prevent systemic dissemination of virus. To understand pDC activation immediately following HIV exposure, cytokine production and maturation of pDCs in response to HIV and a variety of other stimuli was compared. PDCs were found to respond suboptimally to HIV compared to other stimuli, with delayed interferon-alpha production, delayed maturation, and decreased production of inflammatory cytokines. Furthermore, HIV induced inhibitory signaling pathways in pDCs, suggesting subversion of the pDC response by HIV. Finally, different stimuli induced different early and late cytokine profiles, highlighting the complex and stimuli-dependant nature of the pDC response.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/25772 |
| Date | 10 January 2011 |
| Creators | Lo, Calvin Chun Chung |
| Contributors | Ostrowski, Mario |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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