Histopathology of experimental invasive pulmonary aspergillosis in rats: Pathological comparison of pulmonary lesions induced by specific virulent factor deficient mutants

• Published in: Microbial pathogenesis 1999-09, Vol.27 (3), p.123-131
• Main Authors: Shibuya, Kazutoshi, Takaoka, Masayoshi, Uchida, Katsuhisa, Wakayama, Megumi, Yamaguchi, Hideyo, Takahashi, Kei, Paris, Sophie, Latge, Jean-Paul, Naoe, Shiro
• Format: Article
• Language: English
• Subjects: Animals; Aspergillosis - mortality; Aspergillosis - pathology; Aspergillus fumigatus; Aspergillus fumigatus - genetics; Aspergillus fumigatus - pathogenicity; Biological and medical sciences; Cyclophosphamide; Disease Models, Animal; Endopeptidases - deficiency; Experimental mycoses and models; Female; Fundamental and applied biological sciences. Psychology; Immunocompromised Host - drug effects; Immunosuppressive Agents; Infectious diseases; invasive pulmonary aspergillosis, experimental model, pathology, Aspergillus fumigatus, protease, rodlet layer; Lung Diseases, Fungal - mortality; Lung Diseases, Fungal - pathology; Male; Medical sciences; Mice; Mice, Inbred BALB C; Microbiology; Mutation; Mycology; Mycoses; Necrosis; Neutropenia - chemically induced; Pathogenicity, host-agent relations, miscellaneous strains, epidemiology; Rats; Rats, Sprague-Dawley; Virulence
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1006/mpat.1999.0288

To investigate the pathology of invasive pulmonary aspergillosis (IPA) in detail, a new animal model of IPA was used to compare the histological features induced by three different strains of Aspergillus fumigatus; mutants devoided of exocellular protease and rodlet and their parental strain. To produce an experimental pulmonary lesion of IPA closely mimicking the human disease, suspension of agarose beads containing conidiae of A. fumigatus were used as an inocula to fix infallibly the causative agents in alveoli and rats were treated with a low-dose of immunosuppressive drugs to avoid an induction of agranulocytosis in rodents. There was no significant difference in the mortality of mice with an intravenous injection between these three strains. However, IPA model in the study was successful to demonstrate a significant difference in the histological feature of lungs of infected rats. Pulmonary lesions on the fifth day after infection induced by the rodletless mutant were limited and inflammatory responses were weak when compared to those induced by both no exocellular protease mutant as well as their parental strain. The evidence of rodlet layer in conidia of Aspergilli may play an important role in the physiopathology of the disease in eliminating the neutrophils and macrophages of hosts on the early stage of the infection.