Respiratory inflammatory response induced by Aspergillus fumigatus in a rat model

Ref ID: 19369

Author:

G. Desoubeaux,1 M. L. Jourdan,2 L. Valera,3 B. Jardin,3 A. Hem,3
E. Bailly,1 P. Diot1 and J. Chandenier1

Author address:

1CHU de Tours, France; 2CHU de Tours, Service d’H!ematologie
Biologique, Tours, France and 3CNRS UMR 3145 Bio-Rad, Sysdiag
R & D, Montpellier, France

Full conference title:

6th Trends in Medical Mycology 2013

Date: 11 October 2014

Abstract:

Introduction Invasive pulmonary aspergillosis occurs in patients at
risk hospitalized in oncology, haematology and organ-transplantation
departments. The management of this opportunistic mycotic disease
remains problematic in part because of a lack of diagnostic tools. In
order to detect new early diagnostic targets, we have explored by
means of proteomics the inflammatory response against Aspergillus
fumigatus in a rat model.
Method A model of invasive pulmonary aspergillosis in immuno-
compromised rats has been developed in Tours University Hospital
(Chandenier et al., 2009; Desoubeaux and Chandenier, 2012). A
suspension of aspergillar conidia or bacterial lipopolysaccharides
(LPS) was nebulised directly into the trachea of animals. We there-
fore looked for pulmonary proteins, by carrying out two-dimensional
gel electrophoresis on bronchial-alveolar lavage fluids (BAL). A com-
parative analysis of the various 2D-maps generated (“œAspergillus-
induced reaction versus non-specific inflammation”) was performed
by Progenesis SameSpots v. 4.1 software. Putative proteins of inter-
est were then identified by mass spectrometry analysis (MS) querying
NCBI database with the MASCOT search engine. Protein characteri-
sations were confirmed by Western blotting.
Results More than 1,500 spots were observed on 2D-maps for the
two types of population. From this amount of spots, the SameSpots
data processing software isolated 20 spots with a strong statistical
discrimination capacity in the expression level (ANOVA-p < 0.01; q < 0.03; power > 0.8). Among the 16 host-proteins successfully
identified by MS, three were of genuine clinical interest: Apolipopro-
tein AI (Apo AI), Serum amylo€ıd P-component precursor (SAP), and
Inter-alpha-inhibitor H4 heavy-chain (ITIH4) which was character-
ised here for the first time in such an infectious context. Western
blotting confirmed systematically their overabundance in many mur-
ine BAL fluids.
Conclusion This explorative approach allowed us to discover the
proteomic landscape of the inflammatory response in a rat model of
aspergillosis. Besides, our results demonstrated that the concomitant
presence of Apo AI, SAP and ITIH4 in BAL fluids was strongly asso-
ciated with invasive pulmonary aspergillosis in rats. Thus, these 3
proteins could potentially be used as associated biomarkers in screen-
ing tests for aspergillosis.

Figure 1 Comparison of two-dimensional gels for control rats and
rats with aspergillosis, and characterisation of the spots with their
respective level of expression.

Abstract Number: o3.6

Conference Year: 2013

Link to conference website: NULL

New link: NULL

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