<p><italic>Cryptococcus neoformans</italic> is an opportunistic fungal pathogen that initiates infection following inhalation. As a result, the pulmonary immune response provides a first line of defense against <italic>C. neoformans</italic>. Surfactant protein D (SP-D) is an important regulator of pulmonary immune responses and is typically host protective against bacterial and viral respiratory infections. However, SP-D is not protective against <italic>C. neoformans</italic>. This is evidenced by previous work from our laboratory demonstrating that SP-D-deficient mice infected with a highly virulent <italic>C. neoformans</italic> strain (H99 Stud) have a lower fungal burden and live longer compared to wild-type (WT) control animals. We hypothesized that SP-D alters susceptibility to <italic>C. neoformans</italic> by dysregulating the innate pulmonary immune response following infection. For this reason, inflammatory cells and cytokines were compared in the bronchoalveolar lavage fluid from WT and SP-D<super>-/-</super> mice after <italic>C. neoformans</italic> infection. Post-infection, mice lacking SP-D had reduced eosinophil infiltration and IL-5 in lung lavage fluid. To further explore the interplay of SP-D, eosinophils, and IL-5, mice expressing altered levels of eosinophils and/or IL-5 were used to assess the role these innate immune mediators play during the host response to <italic>C. neoformans</italic>. IL-5 overexpressing mice had increased pulmonary eosinophilia and were more susceptible to <italic>C. neoformans</italic> infection as compared to WT mice. Furthermore, the response to <italic>C. neoformans</italic> infection in SP-D<super>-/-</super> mice could be restored to that of WT mice by increasing IL-5 and eosinophils, via crossing the IL-5 transgene onto the SP-D<super>-/-</super> background. Together, these studies support the conclusion that SP-D increases susceptibility to <italic>C. neoformans</italic> infection by promoting <italic>C. neoformans</italic>-driven pulmonary IL-5 and eosinophil infiltration.</p> / Dissertation
| Identifer | oai:union.ndltd.org:DUKE/oai:dukespace.lib.duke.edu:10161/8072 |
| Date | January 2013 |
| Creators | Holmer, Stephanie |
| Contributors | Perfect, John R |
| Source Sets | Duke University |
| Detected Language | English |
| Type | Dissertation |
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