The carbohydrate lectin receptor dectin-1 mediates the immune response to Exserohilum rostratum

Jennifer L. Reedy, Paige E. Negoro, Marianela Feliu, Allison K. Lord, Nida S. Khan, Dan P. Lukason, Nathan P. Wiederholdc, Jenny M. Tam, Michael K. Mansour, Thomas F Patterson, Jatin M. Vyas

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Dematiaceous molds are found ubiquitously in the environment and cause a wide spectrum of human disease, including infections associated with high rates of mortality. Despite this, the mechanism of the innate immune response has been less well studied, although it is key in the clearance of fungal pathogens. Here, we focus on Exserohilum rostratum, a dematiaceous mold that caused 753 infections during a multistate outbreak due to injection of contaminated methylprednisolone. We show that macrophages are incapable of phagocytosing Exserohilum. Despite a lack of phagocytosis, macrophage production of tumor necrosis factor alpha is triggered by hyphae but not spores and depends upon Dectin-1, a C-type lectin receptor. Dectin-1 is specifically recruited to the macrophage-hyphal interface but not the macrophage-spore interface due to differences in carbohydrate antigen expression between these two fungal forms. Corticosteroid and antifungal therapy perturb this response, resulting in decreased cytokine production. In vivo soft tissue infection in wild-type mice demonstrated that Exserohilum provokes robust neutrophilic and granulomatous inflammation capable of thwarting fungal growth. However, coadministration of methylprednisolone acetate results in robust hyphal tissue invasion and a significant reduction in immune cell recruitment. Our results suggest that Dectin-1 is crucial for macrophage recognition and the macrophage response to Exserohilum and that corticosteroids potently attenuate the immune response to this pathogen.

Original languageEnglish (US)
Article numbere00903
JournalInfection and Immunity
Volume85
Issue number3
DOIs
StatePublished - 2017

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Keywords

  • Dectin-1
  • Exserohilum
  • Fungi
  • Macrophages
  • Molds

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Reedy, J. L., Negoro, P. E., Feliu, M., Lord, A. K., Khan, N. S., Lukason, D. P., Wiederholdc, N. P., Tam, J. M., Mansour, M. K., Patterson, T. F., & Vyas, J. M. (2017). The carbohydrate lectin receptor dectin-1 mediates the immune response to Exserohilum rostratum. Infection and Immunity, 85(3), [e00903]. https://doi.org/10.1128/IAI.00903-16