Therapeutic effects of recombinant forms of full-length and truncated human surfactant protein D in a murine model of invasive pulmonary aspergillosis

Mamta Singh, Taruna Madan, Patrick Waters, Sanchaita Sonar, Shiv K. Singh, Mohammad F. Kamran, Andrés López Bernal, P. Usha Sarma, Vijay K. Singh, Erika C. Crouch, Uday Kishore

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17 Scopus citations

Abstract

Aspergillus fumigatus (Afu) is an opportunistic fungal pathogen that can cause fatal invasive pulmonary aspergillosis (IPA) in immunocompromised individuals. Previously, surfactant protein D (SP-D), a surfactant-associated innate immune molecule, has been shown to enhance phagocytosis and killing of Afu conidia by phagocytic cells in vitro. An intranasal treatment of SP-D significantly increased survival in a murine model of IPA. Here we have examined mechanisms via which recombinant forms of full-length (hSP-D) or truncated human SP-D (rhSP-D) offer protection in a murine model of IPA that were immunosuppressed with hydrocortisone and challenged intranasally with Afu conidia prior to the treatment. SP-D or rhSP-D treatment increased the survival rate to 70% and 80%, respectively (100% mortality on day 7 in IPA mice), with concomitant reduction in the growth of fungal hyphae in the lungs, and increased levels of TNF-α and IFN-γ in the lung suspension supernatants, as compared to untreated IPA mice. The level of macrophage inflammatory protein-1α (MIP-1α) in the lung cell suspension was also raised considerably following treatment with SP-D or rhSP-D. Our results appear to reaffirm the notion that under immunocompromised conditions, human SP-D or its truncated form can offer therapeutic protection against fatal challenge with Afu conidia challenge. Taken together, the SP-D-mediated protective mechanisms include enhanced phagocytosis by recruited macrophages and neutrophils and fungistatic properties, suppression of the levels of pathogenic Th2 cytokines (IL-4 and IL-5), enhanced local production of protective Th1 cytokines, TNF-α and IFN-γ, and that of protective C-C chemokine, MIP-1α.

Original languageEnglish
Pages (from-to)2363-2369
Number of pages7
JournalMolecular Immunology
Volume46
Issue number11-12
DOIs
StatePublished - Jul 1 2009
Externally publishedYes

Keywords

  • Aspergillosis
  • Innate immunity
  • Mouse model
  • Surfactant protein D
  • Therapeutics

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    Singh, M., Madan, T., Waters, P., Sonar, S., Singh, S. K., Kamran, M. F., Bernal, A. L., Sarma, P. U., Singh, V. K., Crouch, E. C., & Kishore, U. (2009). Therapeutic effects of recombinant forms of full-length and truncated human surfactant protein D in a murine model of invasive pulmonary aspergillosis. Molecular Immunology, 46(11-12), 2363-2369. https://doi.org/10.1016/j.molimm.2009.03.019