The Impact of Surfactant Protein D, Interleukin-5, and Eosinophilia on Cryptococcosis.
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 C. neoformans 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. Thus 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 have 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 infected with C. neoformans to assess the role of these innate immune mediators. IL-5 overexpressing mice have increased pulmonary eosinophilia and are more susceptible to C. neoformans infection as compared to WT mice. Furthermore, susceptibility of SP-D(-/-) mice to C. neoformans infection could be restored to that of WT mice by increasing IL-5 and eosinophils, via crossing the IL-5 overexpressing mice with SP-D(-/-) mice. 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.
Holmer, SM; Evans, KS; Asfaw, YG; Saini, D; Schell, WA; Ledford, JG; Frothingham, R; Wright, JR; Sempowski, GD; Perfect, JR
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