Aspergillus fumigatus allergen expression is coordinately regulated in response to hydrogen peroxide and cyclic AMPReportar como inadecuado




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Clinical and Molecular Allergy

, 8:15

First Online: 03 November 2010Received: 30 June 2010Accepted: 03 November 2010

Abstract

BackgroundA. fumigatus has been associated with a wide spectrum of allergic disorders such as ABPA or SAFS. It is poorly understood what allergens in particular are being expressed during fungal invasion and which are responsible for stimulation of immune responses. Study of the dynamics of allergen production by fungi may lead to insights into how allergens are presented to the immune system.

MethodsExpression of 17 A. fumigatus allergen genes was examined in response to various culture conditions and stimuli as well as in the presence of macrophages in order to mimic conditions encountered in the lung.

ResultsExpression of 14-17 allergen genes was strongly induced by oxidative stress caused by hydrogen peroxide Asp f 1 -2 -4 -5 -6 -7 -8 -10 -13 -17 and -18, all >10-fold and Asp f 11 -12, and -22, 5-10-fold and 16-17 allergen genes were repressed in the presence of cAMP. The 4 protease allergen genes Asp f -5 -10 -13 and -18 were expressed at very low levels compared to the comparator β-tubulin under all other conditions examined. Mild heat shock, anoxia, lipid and presence of macrophages did not result in coordinated changes in allergen gene expression. Growth on lipid as sole carbon source contributed to the moderate induction of most of the allergen genes. Heat shock 37°C > 42°C caused moderate repression in 11-17 genes Asp f 1 -2 -4 -5 -6 -9 -10 -13 -17 -18 and -23 2- to 9-fold, which was mostly evident for Asp f 1 and -9 ~9-fold. Anaerobic stress led to moderate induction of 13-17 genes 1.1 to 4-fold with one, Asp f 8 induced over 10-fold when grown under mineral oil. Complex changes were seen in gene expression during co-culture of A. fumigatus with macrophages.

ConclusionsRemarkable coordination of allergen gene expression in response to a specific condition oxidative stress or the presence of cAMP has been observed, implying that a single biological stimulus may play a role in allergen gene regulation. Interdiction of a putative allergen expression induction signalling pathway might provide a novel therapy for treatment of fungal allergy.

Electronic supplementary materialThe online version of this article doi:10.1186-1476-7961-8-15 contains supplementary material, which is available to authorized users.

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Autor: Marcin G Fraczek - Rifat Rashid - Marian Denson - David W Denning - Paul Bowyer

Fuente: https://link.springer.com/







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