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

Désoubeaux, Guillaume; Cray, Carolyn

doi:10.3389/fmicb.2017.00841

Cited by 50 publications

(39 citation statements)

References 491 publications

(754 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For the neutropenic model, mice were treated with cyclophosphamide, an alkylating drug that causes profound neutropenia as well as with triamcinolone acetate, a corticosteroid that affects alveolar macrophages function, then reducing the first barrier to pulmonary infection. This model mimics the infection in profoundly neutropenic patients, like those undergoing leukaemia (Desoubeaux & Cray, ). In a separate experiment, a non‐neutropenic model, consisting only of corticosteroid administration, was employed.…”

Section: Resultsmentioning

confidence: 99%

SH3‐class Ras guanine nucleotide exchange factors are essential forAspergillus fumigatusinvasive growth

Martín‐Vicente

Souza

Abdallah

et al. 2019

Cellular Microbiology

View full text Add to dashboard Cite

Proper hyphal morphogenesis is essential for the establishment and progression of invasive disease caused by filamentous fungi. In the human pathogen Aspergillus fumigatus, signalling cascades driven by Ras and Ras‐like proteins orchestrate a wide variety of cellular processes required for hyphal growth. For activation, these proteins require interactions with Ras‐subfamily‐specific guanine nucleotide exchange factors (RasGEFs). Although Ras‐protein networks are essential for virulence in all pathogenic fungi, the importance of RasGEF proteins is largely unexplored. A. fumigatus encodes four putative RasGEFs that represent three separate classes of RasGEF proteins (SH3‐, Ras guanyl nucleotide‐releasing protein [RasGRP]–, and LTE‐class), each with fungus‐specific attributes. Here, we show that the SH3‐class and RasGRP‐class RasGEFs are required for properly timed polarity establishment during early growth and branch emergence as well as for cell wall stability. Further, we show that SH3‐class RasGEF activity is essential for polarity establishment and maintenance, a phenotype that is, at least, partially independent of the major A. fumigatus Ras proteins, RasA and RasB. Finally, loss of both SH3‐class RasGEFs resulted in avirulence in multiple models of invasive aspergillosis. Together, our findings suggest that RasGEF activity is essential for the integration of multiple signalling networks to drive invasive growth in A. fumigatus.

show abstract

Section: Resultsmentioning

confidence: 99%

SH3‐class Ras guanine nucleotide exchange factors are essential forAspergillus fumigatusinvasive growth

Martín‐Vicente

Souza

Abdallah

et al. 2019

Cellular Microbiology

View full text Add to dashboard Cite

show abstract

“…In mice, as in humans, immunosuppression renders the host susceptible to IPA. To model disease, various immunosuppressive regimens are established, and their use is strongly based on the exact research question (for a review see [13]). The two most prominent immunosuppression models render the mice either leukopenic (usually with alkylating agents), which aims to mimic profoundly neutropenic patients (e.g.…”

Section: Resultsmentioning

confidence: 99%

3D light sheet fluorescence microscopy of lungs to dissect local host immune -Aspergillus fumigatusinteractions

Amich

Mokhtari

Strobel

et al. 2019

Preprint

View full text Add to dashboard Cite

Rudolf-Virchow-Zentrum für Experimentelle Biomedizin. 35 Universität Würzburg. 36 Josef-Schneider-Straße 2, Haus D15. D -97080 Würzburg 37 38 39 40 41 42 43 44 45 VISUAL ABSTRACT 46 Quantitative light sheet fluorescence microscopy to dissect local host-pathogen interactions 47 ABSTRACT 51Aspergillus fumigatus is an opportunistic fungal pathogen that can cause life-threatening 52 invasive lung infections in immunodeficient patients. The cellular and molecular processes of 53 infection during onset, establishment and progression are highly complex and depend on 54 both fungal attributes and the immune status of the host. Therefore, preclinical animal 55 models are paramount to investigate and gain better insight into the infection process. Yet, 56 despite their extensive use, commonly employed murine models of invasive pulmonary 57 aspergillosis are not well understood due to analytical limitations. Here we present 58 quantitative light sheet fluorescence microscopy (LSFM) to describe fungal growth and the 59 local immune response in whole lungs at cellular resolution within its anatomical context. We 60 analyzed three very common murine models of pulmonary aspergillosis based on 61 immunosuppression with corticosteroids, chemotherapy-induced leukopenia or 62 myeloablative irradiation. LSFM uncovered distinct architectures of fungal growth and 63 degrees of tissue invasion in each model. Furthermore, LSFM revealed the spatial 64 distribution, interaction and activation of two key immune cell populations in antifungal 65 defense: alveolar macrophages and polymorphonuclear neutrophils. Interestingly, the 66 patterns of fungal growth correlated with the detected effects of the immunosuppressive 67 regimens on the local immune cell populations. Moreover, LSFM demonstrates that the 68 commonly used intranasal route of spore administration did not result in the desired intra-69 alveolar deposition, as more than 60% of fungal growth occurred outside of the alveolar 70 space. Hence, LSFM allows for more rigorous characterization of murine models of invasive 71 pulmonary aspergillosis and pinpointing their strengths and limitations. 72 IMPORTANCE 73The use of animal models of infection is essential to advance our understanding of complex 74 host-pathogen interactions that take place during Aspergillus fumigatus lung infections. As in 75 the case of humans, mice need to be immunosuppressed to become susceptible to invasive 76 pulmonary aspergillosis, the most serious infection caused by A. fumigatus. There are 77 several immunosuppressive regimens that are routinely used to investigate fungal growth 78 and/or immune responses in murine models of invasive pulmonary aspergillosis (IPA). 79However, the precise consequences that each immunosuppressive model has on the local 80 immune populations and for fungal growth are not completely understood. Here we 81 employed light sheet fluorescence microscopy (LSFM) to analyze whole lungs at cellular 82 resolution, to pin down the scenario commonly used IPA models. Our results will be ...

show abstract

“…(24). Aspergillus fumigatus is the most common and life-threatening ubiquitous airborne opportunistic fungal pathogen, especially significant among immunocompromised hosts (15,26).It is present in the environment, particularly in air, water, plants and soil (1,20) When its conidia are inhaled, it can be responsible for wide range of distinct clinical entities (8). The ability of this species to cause different types of diseases is due to possess various virulence factors which help with fungal survival and persistence in the host resulting in tissue damage and disease (7).…”

Section: Intoductionmentioning

confidence: 99%

Comparative Study of Pathogenicity Between Aspergillus Fumigatus and Penicillium Chrysogenum in Mice

Yassein¹

2020

Iraqi J. Agric. Sci.

View full text Add to dashboard Cite

This study was conducted to compare between two types of opportunistic fungi (Aspergillus fumigatus and Penicillium chrysogenum) in concerning their pathogenicity after intraperitoneal inoculation of mice. A total of twenty four male albino mice were used in this study which divided equally into 3 groups, The first and second groups were inoculated with 0.2ml of 1x 107spores/ml of A. fumigatus and P. chrysogenum intraperitonially respectively, while the third group was inoculated with normal saline which served as control group. All animals were monitored for 2 weeks after infection. The blood samples were collected by heart puncture after 18 days post infection to isolate of serum that used for biochemical analysis of liver and kidney functions. After that, all animals were sacrificed. Some internal organs of infected groups (liver, kidney, intestine, heart, spleen and lung) were taken to study the histopathological changes. It was found that there was severe histopathological changes in studied organs of infected mice particularly liver, kidney, spleen and intestine which corresponding with significant variation (p<0.01) in enzyme activities of liver and kidney like (Alanine Aminotransferase (ALT), Urea and Creatinine). Also, It was found that P. chrysogenum had more impact on these enzymes (15.65 ± 0.78, 135.23 ± 8.75 and 0.928 ± 0.02 respectively) than A. fumigatus (21.70 ± 1.04, 57.91 ± 5.99 and 0.587 ± 0.03 respectively). Therefore, the present study indicated that fungi present in the environment can induce severe inflammation reach to tissue damage in most vital internal organs So, further studies should be performed to determine the specific virulence factors and active components, which are responsible for pathogenesis of A. fumigatus and P. chrysogenum in spite of the fact that P. chrysogenum can produce antibiotic.

show abstract

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

Cited by 50 publications

References 491 publications

SH3‐class Ras guanine nucleotide exchange factors are essential forAspergillus fumigatusinvasive growth

SH3‐class Ras guanine nucleotide exchange factors are essential forAspergillus fumigatusinvasive growth

3D light sheet fluorescence microscopy of lungs to dissect local host immune -Aspergillus fumigatusinteractions

Comparative Study of Pathogenicity Between Aspergillus Fumigatus and Penicillium Chrysogenum in Mice

Contact Info

Product

Resources

About