Rodent Models of Invasive Aspergillosis due to Aspergillus fumigatus: Still a Long Path toward Standardization.

Guillaume Desoubeaux,Carolyn Cray

doi:10.3389/fmicb.2017.00841

Abstract

Invasive aspergillosis has been studied in laboratory by the means of plethora of distinct animal models. They were developed to address pathophysiology, therapy, diagnosis, or miscellaneous other concerns associated. However, there are great discrepancies regarding all the experimental variables of animal models, and a thorough focus on them is needed. This systematic review completed a comprehensive bibliographic analysis specifically-based on the technical features of rodent models infected with Aspergillus fumigatus. Out the 800 articles reviewed, it was shown that mice remained the preferred model (85.8% of the referenced reports), above rats (10.8%), and guinea pigs (3.8%). Three quarters of the models involved immunocompromised status, mainly by steroids (44.4%) and/or alkylating drugs (42.9%), but only 27.7% were reported to receive antibiotic prophylaxis to prevent from bacterial infection. Injection of spores (30.0%) and inhalation/deposition into respiratory airways (66.9%) were the most used routes for experimental inoculation. Overall, more than 230 distinct A. fumigatus strains were used in models. Of all the published studies, 18.4% did not mention usage of any diagnostic tool, like histopathology or mycological culture, to control correct implementation of the disease and to measure outcome. In light of these findings, a consensus discussion should be engaged to establish a minimum standardization, although this may not be consistently suitable for addressing all the specific aspects of invasive aspergillosis.

Highlights

Aspergillosis is an airborne fungal infection due to ubiquitous molds belonging to the genus Aspergillus
The authors exhaustively reviewed the retained articles. They thoroughly focused on the pivotal experimental parameters and the major technical features that are assumed to likely influence the results (Schmidt, 2002; Clemons and Stevens, 2005; Lewis and Wiederhold, 2005; Patterson, 2005; Capilla et al, 2007): rodent species and strains as well as their weight and sex, the immunosuppressive regimen they underwent, the A. fumigatus strain(s) and the fungal inoculum used for the experimental challenge, the route of inoculation, the clinical, and biological parameters to follow up to assert correct implementation of the disease and its monitoring (Figure 1)
A perfect unique model, i.e., highly reproducible, economical and standardized, should be expected to address reproducibly all these issues (Najvar et al, 2004; Patterson, 2005). This present overview attempted to summarize all the technical parameters reported in the literature about rodent models of invasive infection caused by A. fumigatus, but was not intended to detail the wealth of insight gained from them into the pathogenis, host immune response, diagnosis, and treatment, and the reader is invited to refer to other publications (Sable et al, 2008; Brown, 2011; Steele and Wormley, 2012; Wüthrich et al, 2012; Drew et al, 2013; Lanternier et al, 2013)

Summary

Introduction

Aspergillosis is an airborne fungal infection due to ubiquitous molds belonging to the genus Aspergillus. For animal models studying invasive aspergillosis (Mahajan et al, 1978; Ghori and Edgar, 1979; Chaudhary and Singh, 1983; Chaudhary et al, 1988; Chilvers et al, 1989; Andriole et al, 1992; Kurtz et al, 1995; Leenders et al, 1996; Richard et al, 1996; Cicogna et al, 1997; Kirkpatrick et al, 2000b; Clemons and Stevens, 2005; Gavaldà et al, 2005; Lewis and Wiederhold, 2005; Patterson, 2005; Chandenier et al, 2009), heterogeneity has always been great regarding their technical variables, like the species or strains to be used, the animal sex and weight, the immunosuppressive regimen, the route of experimental infection, the fungal inoculum size, and the methods to assess fungal burden (Hohl, 2014). One can notice that rodents have been mostly used so far, because they are of small size, inexpensive, easy-to-handle, and the ready availability of reagents and methods (Andriole et al, 1992; Clemons and Stevens, 2005; Lewis and Wiederhold, 2005; Patterson, 2005; Paulussen et al, 2014)

Methods

Results

Conclusion