Impaired interferon-gamma responses, increased interleukin-17 expression, and a tumor necrosis factor-alpha transcriptional program in invasive aspergillosis.
J Infect Dis
; 200(8): 1341-51, 2009 Oct 15.
Article
en En
| MEDLINE
| ID: mdl-19754306
ABSTRACT
BACKGROUND:
Invasive aspergillosis (IA) is the most common cause of death associated with fungal infection in the developed world. Historically, susceptibility to IA has been associated with prolonged neutropenia; however, IA has now become a major problem in patients on calcineurin inhibitors and allogenic hematopoietic stem cell transplant patients following engraftment. These observations suggest complex cellular mechanisms govern immunity to IA.METHODS:
To characterize the key early events that govern outcome from infection with Aspergillus fumigatus, we performed a comparative immunochip microarray analysis of the pulmonary transcriptional response to IA between cyclophosphamide-treated mice and immunocompetent mice at 24 h after infection.RESULTS:
We demonstrate that death due to infection is associated with a failure to generate an incremental interferon-gamma response, increased levels of interleukin-5 and interleukin-17a transcript, coordinated expression of a network of tumor necrosis factor-alpha-related genes, and increased levels of tumor necrosis factor-alpha. In contrast, clearance of infection is associated with increased expression of a number genes encoding proteins involved in innate pathogen clearance, as well as apoptosis and control of inflammation.CONCLUSION:
This first organ-level immune response transcriptional analysis for IA has enabled us to gain new insights into the mechanisms that govern fungal immunity in the lung.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Interferón gamma
/
Factor de Necrosis Tumoral alfa
/
Interleucina-17
/
Aspergilosis Pulmonar
Límite:
Animals
Idioma:
En
Revista:
J Infect Dis
Año:
2009
Tipo del documento:
Article
País de afiliación:
Reino Unido