Hypoxia enhances innate immune activation to Aspergillus fumigatus through cell wall modulation.
Microbes Infect
; 15(4): 259-69, 2013 Apr.
Article
em En
| MEDLINE
| ID: mdl-23220005
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 ß-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 ß-glucan receptor dectin-1. In a corticosteroid model of invasive pulmonary aspergillosis, A. fumigatus ß-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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Aspergillus fumigatus
/
Parede Celular
/
Lectinas Tipo C
/
Imunidade Inata
Limite:
Animals
Idioma:
En
Revista:
Microbes Infect
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
MICROBIOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos