The Impact of Surfactant Protein D, Interleukin‑5, and Eosinophilia on Cryptococcosis

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2013

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Abstract

Cryptococcus neoformans is an opportunistic fungal pathogen that initiates infection following inhalation. As a result, the pulmonary immune response provides a first line of defense against C. neoformans. 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 C. neoformans. This is evidenced by previous work from our laboratory demonstrating that SP-D-deficient mice infected with a highly virulent C. neoformans 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 C. neoformans 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-/- mice after C. neoformans 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 C. neoformans. IL-5 overexpressing mice had increased pulmonary eosinophilia and were more susceptible to C. neoformans infection as compared to WT mice. Furthermore, the response to C. neoformans infection in SP-D-/- 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-/- background. Together, these studies support the conclusion that SP-D increases susceptibility to C. neoformans infection by promoting C. neoformans-driven pulmonary IL-5 and eosinophil infiltration.

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Holmer, Stephanie (2013). The Impact of Surfactant Protein D, Interleukin‑5, and Eosinophilia on Cryptococcosis. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/8072.

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