title: Factors affecting the course and severity of transnasally induced Staphylococcus aureus pneumonia in mice.
abstract: In order to examine several factors that may affect the course and severity of transnasally induced Staphylococcus aureus pneumonia in mice, bacteria were prepared in a free suspension or bound to fetal mouse cells. Immunosuppression was induced in five strains of mice (ICR, C57BL/6, BALB/c, C3H/He and CBA/J) by injection of cyclophosphamide (200 mg/kg body weight), 2 days before infection. Impairment of mucociliary clearance was induced by intranasal instillation of formalin. Mice were then infected with various doses and strains of the organism. Although no significant differences were observed between either form of inoculum, pretreatment with formalin plus cyclophosphamide was associated with a significant increase in lung bacterial counts. In particular, cyclophosphamide treatment was associated with a high mortality in mice infected with several strains of S. aureus irrespective of their toxin production profiles. Histopathological examination demonstrated that in mice treated with formalin plus cyclophosphamide, clusters of bacteria were observed in lung parenchyma, associated with a mild accumulation of inflammatory cells at day 2 and extensive cell infiltration at day 7. CBA/J mice represented the most susceptible strain among those examined, with 10(4)- and 10(2)-fold higher bacterial counts in the lungs at days 3 and 5, respectively. These results indicate that neutropenia and impaired mucociliary clearance are major factors that influence the severity of S. aureus pneumonia in mice. Analysis of the role of genetic background in enhancement of vulnerability to infection is warranted in future studies.
authors.affiliation: First Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Department of Microbiology, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Miyazaki
authors.affiliation: Department of Microbiology, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tateda
authors.affiliation: Department of Microbiology, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Pathology, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Shirou
authors.initials: S
authors.lastname: Tsujimoto
authors.affiliation: Department of Microbiology, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D015169:Colony Count, Microbial; D003520:Cyclophosphamide / Q000009:adverse effects; D004195:Disease Models, Animal; D004202:Disinfectants / Q000009:adverse effects; D005557:Formaldehyde / Q000009:adverse effects; D020022:Genetic Predisposition to Disease; D007166:Immunosuppressive Agents / Q000009:adverse effects; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008813:Mice, Inbred ICR; D009079:Mucociliary Clearance / Q000187:drug effects; D009503:Neutropenia / Q000139:chemically induced; D011023:Pneumonia, Staphylococcal / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D013211:Staphylococcus aureus / Q000254:growth & development / Q000502:physiology*
chemical_list: D004202:Disinfectants; D007166:Immunosuppressive Agents; D005557:Formaldehyde; D003520:Cyclophosphamide