Factors affecting the course and severity of transnasally induced Staphylococcus aureus pneumonia in mice

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. Immunosup pression 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 intra nasal instillation of formalin, Mice were then infected with various doses and strains of the organism. Although no significant differences were obser ved between either form of inoculum, pretreatment with formalin plus cyclop hosphamide was associated with a significant increase in lung bacterial cou nts. In particular, cyclophosphamide treatment was associated with a high m ortality in mice infected with several strains of S. aureus irrespective of their toxin production profiles. Histopathological examination demonstrate d that in mice treated with formalin plus cyclophosphamide, clusters of bac teria were observed in lung parenchyma, associated with a mild accumulation of inflammatory cells at day 2 and extensive cell infiltration at day 7. C BA/J mice represented the most susceptible strain among those examined, wit h 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 mucoc iliary clearance are major factors that influence the severity of S, aureus pneumonia in mice. Analysis of the role of genetic background in enhanceme nt of vulnerability to infection is warranted in future studies.