Impact of surfactant protein D, interleukin-5, and eosinophilia on Cryptococcosis.

Journal Article (Journal Article)

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 than 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. Postinfection, mice lacking SP-D have reduced eosinophil infiltration and interleukin-5 (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 than WT mice. Furthermore, susceptibility of SP-D(-/-) mice to C. neoformans infection could be restored to the level of WT mice by increasing IL-5 and eosinophils by 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.

Full Text

Duke Authors

Cited Authors

  • Holmer, SM; Evans, KS; Asfaw, YG; Saini, D; Schell, WA; Ledford, JG; Frothingham, R; Wright, JR; Sempowski, GD; Perfect, JR

Published Date

  • February 2014

Published In

Volume / Issue

  • 82 / 2

Start / End Page

  • 683 - 693

PubMed ID

  • 24478083

Pubmed Central ID

  • PMC3911392

Electronic International Standard Serial Number (EISSN)

  • 1098-5522

Digital Object Identifier (DOI)

  • 10.1128/IAI.00855-13


  • eng

Conference Location

  • United States