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

Stephanie M. Holmer, Kathy S. Evans, Yohannes G. Asfaw, Divey Saini, Wiley A. Schell, Julie G. Ledford, Richard Frothingham, Jo Rae Wright, Gregory D. Sempowski, John R. Perfect

Research output: Contribution to journalArticle

23 Scopus citations

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 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

Original languageEnglish (US)
Pages (from-to)683-693
Number of pages11
JournalInfection and Immunity
Volume82
Issue number2
DOIs
StatePublished - Feb 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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    Holmer, S. M., Evans, K. S., Asfaw, Y. G., Saini, D., Schell, W. A., Ledford, J. G., Frothingham, R., Wright, J. R., Sempowski, G. D., & Perfect, J. R. (2014). Impact of surfactant protein D, interleukin-5, and eosinophilia on cryptococcosis. Infection and Immunity, 82(2), 683-693. https://doi.org/10.1128/IAI.00855-13