The pathogenesis of experimental pulmonary aspergillosis in normal and cortisone‐treated rats

Turner, Keven J.; Hackshaw, R.; Papadimitriou, John; Perrott, John K.

doi:10.1002/path.1711180202

Cited by 17 publications

(4 citation statements)

References 8 publications

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“…Immunosuppressive drugs. It has been known for a long time that down-regulation of the immune system as a result of immunosuppressive drugs triggers the development of invasive aspergillosis in experimental animal models as well as in naturally occurring human infections (61,93,579,668,724). The alterations of the anti-A.…”

Section: Role Of Immunosuppression In the Development Of Invasive Aspmentioning

confidence: 99%

Aspergillus fumigatusand Aspergillosis

1999

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SUMMARY Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic fungi. Humans and animals constantly inhale numerous conidia of this fungus. The conidia are normally eliminated in the immunocompetent host by innate immune mechanisms, and aspergilloma and allergic bronchopulmonary aspergillosis, uncommon clinical syndromes, are the only infections observed in such hosts. Thus, A. fumigatus was considered for years to be a weak pathogen. With increases in the number of immunosuppressed patients, however, there has been a dramatic increase in severe and usually fatal invasive aspergillosis, now the most common mold infection worldwide. In this review, the focus is on the biology of A. fumigatus and the diseases it causes. Included are discussions of (i) genomic and molecular characterization of the organism, (ii) clinical and laboratory methods available for the diagnosis of aspergillosis in immunocompetent and immunocompromised hosts, (iii) identification of host and fungal factors that play a role in the establishment of the fungus in vivo, and (iv) problems associated with antifungal therapy.

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Section: Role Of Immunosuppression In the Development Of Invasive Aspmentioning

confidence: 99%

Aspergillus fumigatusand Aspergillosis

1999

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“…Cortisone lowers the normally high resistance of laboratory animals to invasive aspergillosis (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). For example, mice become extremely susceptible to aspergillosis after large doses of cortisone (13,14,23,24), but not after myelosuppression or neutropenia (14,23).…”

mentioning

confidence: 99%

Selective Protection against Conidia by Mononuclear and against Mycelia by Polymorphonuclear Phagocytes in Resistance to Aspergillus

Schaffner¹,

Douglas²,

Braude³

1982

J. Clin. Invest.

581

411

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A B S T R A C T By comparing natural immunity to Aspergillus fumigatus (AF) in vivo with the action of human or mouse phagocytes against AF in vitro, we delineated two sequential lines of defense against AF. The first line of defense was formed by macrophages and directed against spores. Macrophages prevented germination and killed spores in vitro and rapidly eradicated conidia in vivo, even in neutropenic and athymic mice. The second was the neutrophilic granulocyte (PMN), which protected against the hyphal form of AF. Human and mouse PMN killed mycelia in vitro. Normal, but not neutropenic mice, stopped hyphal growth, and eradicated mycelia. Either line of defense acting alone protected mice from high challenge doses. Natural immunity collapsed only when both the reticuloendothelial system and PMN were impaired. These findings are in keeping with the clinical observation that high doses of cortisone and neutropenia are the main risk factors for invasive aspergillosis. Cortisone inhibited the conidiacidal activity of mouse macrophages in vivo and of human or mouse mononuclear phagocytes in vitro. Cortisone damaged this first line of defense directly and not through the influence of T lymphocytes or other systems modifying macrophage function as shown in athymic mice and in vitro. In addition, daily high doses of cortisone in mice reduced the mobilization of PMN so that the second line of defense was also impaired. Thus, cortisone can break down natural resistance on its own. Myelosuppression rendered mice susceptible only when the first line of defense was overpowered by high chal-

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“…Altogether, the frequency of spore administration to induce experimental infection was generally based on a single application, except for some specific studies that performed daily inoculations over 2 or 3 days (or even over a longer period; Smith et al, 1994; Cenci et al, 1998, 1999, 2000, 2001, 2002; Del Sero et al, 1999; Bozza et al, 2002a; Du et al, 2002; Bellocchio et al, 2004a,b, 2005; Gaziano et al, 2004; Mellado et al, 2005; Shao et al, 2005a; Mazaki et al, 2006; Zelante et al, 2007, 2009, 2015; D'Angelo et al, 2009; Morton et al, 2010, 2012; Moretti et al, 2012, 2014; Zhang et al, 2013; Hein et al, 2015), or repeated spaced administrations (Smith, 1972, 1973, 1977; Turner et al, 1975a,b; Morton et al, 2012; Turner et al, 1976; Lehmann and White, 1976; de Repentigny et al, 1993; Cenci et al, 1997; Mazaki et al, 2006; Fei et al, 2011; Templeton et al, 2011; Alcazar-Fuoli et al, 2015; Savers et al, 2016), sometimes in order to induce immune protection (Centeno-Lima et al, 2002) or to enhance the infection yields, particularly for inhalational models in chamber (Buskirk et al, 2014). …”

Section: Resultsmentioning

confidence: 99%

“…Detection of anti- Aspergillus antibodies was sometimes performed (Turner et al, 1975b, 1976; Naik et al, 2011). In human medicine it is nonetheless not considered as a biomarker of invasive infection, but rather of chronic or allergic aspergillosis.…”

Section: Resultsmentioning

confidence: 99%

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

Désoubeaux

Cray

2017

Front. Microbiol.

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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.

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The pathogenesis of experimental pulmonary aspergillosis in normal and cortisone‐treated rats

Cited by 17 publications

References 8 publications

Aspergillus fumigatusand Aspergillosis

Aspergillus fumigatusand Aspergillosis

Selective Protection against Conidia by Mononuclear and against Mycelia by Polymorphonuclear Phagocytes in Resistance to Aspergillus

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

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