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Plasmacytoid dendritic cell-derived IFNa modulates Th17 differentiation during Bordetella pertussis infection in mice
Thesis - Campus Access Only
Master of Science (MS)
Whooping cough, caused by Bordetella pertussis (B. pertussis), is a highly contagious respiratory disease. T-helper 17 (Th17) cells have been implicated in host defense and control of mucosal pathogens, including B. pertussis. Type I Interferon (IFN) has recently been documented to inhibit Th17 differentiation and IL-17 production. Type I IFN has been well characterized as an antiviral cytokine, but recent studies linking it to the inhibition of Th17 differentiation have led to investigation of whether type I IFN may be detrimental during bacterial infections. Plasmacytoid dendritic cells (pDCs) are known as the most potent producers of type I IFN. pDCs are activated during lung inflammation in response to pathogens, but their role during B. pertussis infection is understudied. Using a murine infection model of B. pertussis, we tested the hypothesis that the functions of pDCs can manipulate the rise of Th17 cells during infection. We used multicolor flow cytometry to characterize the immune cells in our infection model and to study the effects of IFNa on Th17 differentiation. In addition, we exposed dendritic cells and CD4+ T cells to IFNa in vitro, and employed pDC- blocking and depleting antibodies in vivo. Lung Th17 cells increased significantly in B. pertussis-infected mice only at 10 days post-infection (dpi) and later. However, lung pDCs secreting IFNa preceded the Th17 rise and emerged 4-5 fold at 5 dpi. In addition, blocking IFNa production in mice restored an early increase in Th17 cells during B. pertussis infection. The recruitment and cytokine secretion of lung pDCs during infection with B. pertussis correlate with the delayed Th17 responses, suggesting a role for pDCs in Th17 differentiation that may account for a longer-lasting disease.
Wu, Victoria, "Plasmacytoid dendritic cell-derived IFNa modulates Th17 differentiation during Bordetella pertussis infection in mice" (2014). Master's Theses. 4521.