Aspergillus fumigatus triggers inflammatory responses by stage-specific β-glucan display

Tobias M. Hohl, Heather L. Van Epps, Amariliz Rivera, Laura A. Morgan, Patrick L. Chen, Marta Feldmesser, Eric G. Pamer

Research output: Contribution to journalArticle

316 Scopus citations

Abstract

Inhalation of fungal spores (conidia) occurs commonly and, in specific circumstances, can result in invasive disease. We investigated the murine inflammatory response to conidia of Aspergillus fumigatus, the most common invasive mold in immunocompromised hosts. In contrast to dormant spores, germinating conidia induce neutrophil recruitment to the airways and TNF-α/MIP-2 secretion by alveolar macrophages. Fungal β-glucans act as a trigger for the induction of these inflammatory responses through their time-dependent exposure on the surface of germinating conidia. Dectin-1, an innate immune receptor that recognizes fungal β-glucans, is recruited in vivo to alveolar macrophage phagosomes that have internalized conidia with exposed β-glucans. Antibody-mediated blockade of Dectin-1 partially inhibits TNF-α/ MIP-2 induction by metabolically active conidia. TLR-2- and MyD88-mediated signals provide an additive contribution to macrophage activation by germinating conidia. Selective responsiveness to germinating conidia provides the innate immune system with a mechanism to restrict inflammatory responses to metabolically active, potentially invasive fungal spores.

Original languageEnglish (US)
Article numbere30
Pages (from-to)232-240
Number of pages9
JournalPLoS pathogens
Volume1
Issue number3
DOIs
StatePublished - 2005

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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    Hohl, T. M., Van Epps, H. L., Rivera, A., Morgan, L. A., Chen, P. L., Feldmesser, M., & Pamer, E. G. (2005). Aspergillus fumigatus triggers inflammatory responses by stage-specific β-glucan display. PLoS pathogens, 1(3), 232-240. [e30]. https://doi.org/10.1371/journal.ppat.0010030