Please use this identifier to cite or link to this item: http://buratest.brunel.ac.uk/handle/2438/8828
Title: Impaired interferon-γ responses, increased interleukin-17 expression, and a tumor necrosis factor–α transcriptional program in invasive aspergillosis
Authors: Armstrong-James, DP
Turnbull, SA
Teo, I
Stark, J
Rogers, NJ
Rogers, TRF
Bignell, E
Haynes, K
Keywords: Invasive aspergillosis;Fungal infection;Tumor necrosis;Calcineurin inhibitors;Allogenic hematopoetic stem cell transplant
Issue Date: 2009
Publisher: Oxford University Press
Citation: The Journal of Infectious Diseases, 200(8), 1341-1351, 2009
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 hematopoetic 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-γ response, increased levels of interleukin-5 and interleukin-17a transcript, coordinated expression of a network of tumor necrosis factor–α-related genes, and increased levels of tumor necrosis factor–α. 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.
Description: This article is available open access through the publisher’s website. Copyright @ 2009 Oxford University Press.
URI: http://jid.oxfordjournals.org/content/200/8/1341
http://bura.brunel.ac.uk/handle/2438/8828
DOI: http://dx.doi.org/10.1086/605931
ISSN: 1537-6613
Appears in Collections:Biological Sciences
Dept of Life Sciences Research Papers

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