Hypoxia enhances innate immune activation to Aspergillus fumigatus through cell wall modulation

Kelly M. Shepardson, Lisa Y. Ngo, Vishukumar Aimanianda, Jean Paul Latgé, Bridget M. Barker, Sara J. Blosser, Yoichiro Iwakura, Tobias M. Hohl, Robert A. Cramer

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Infection by the human fungal pathogen Aspergillus fumigatus induces hypoxic microenvironments within the lung that can alter the course of fungal pathogenesis. How hypoxic microenvironments shape the composition and immune activating potential of the fungal cell wall remains undefined. Herein we demonstrate that hypoxic conditions increase the hyphal cell wall thickness and alter its composition particularly by augmenting total and surface-exposed β-glucan content. In addition, hypoxia-induced cell wall alterations increase macrophage and neutrophil responsiveness and antifungal activity as judged by inflammatory cytokine production and ability to induce hyphal damage. We observe that these effects are largely dependent on the mammalian β-glucan receptor dectin-1. In a corticosteroid model of invasive pulmonary aspergillosis, A. fumigatus β-glucan exposure correlates with the presence of hypoxia in situ. Our data suggest that hypoxia-induced fungal cell wall changes influence the activation of innate effector cells at sites of hyphal tissue invasion, which has potential implications for therapeutic outcomes of invasive pulmonary aspergillosis.

Original languageEnglish (US)
Pages (from-to)259-269
Number of pages11
JournalMicrobes and Infection
Volume15
Issue number4
DOIs
StatePublished - Apr 2013
Externally publishedYes

Keywords

  • Aspergillus fumigatus
  • Beta-glucan
  • Cell wall
  • Fungal pathogenesis
  • Hypoxia

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases

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