Murine mechanisms of resistance to Streptococcus pneumoniae

The aim of this thesis was to investigate the basis of genetic resistance or susceptibility to infection with S. pneumoniae using a mouse model of bronchopneumonia. To this end, a panel of strains of inbred mice was intranasally infected with S. pneumoniae type 2 strain (D39), and type 3 (GB05). BALB/c mice were resistant and CBA/Ca were susceptible to infection, particularly with D39 pneumococci. To analyse the genetic inheritance, filial generations (F1 mice and F2 mice) were produced from intercross breeding these two strains and subsequently challenged with D39 pneumococci.;Further investigation of the parental strains using D39 pneumococci revealed that BALB/c mice, unlike CBA/Ca mice, were able to prevent proliferation of pneumococci in lungs and blood. Rapidly increasing numbers of bacteria in the blood was a feature of CBA/Ca, in contrast to BALB/c.;Analysis of the cellular response to infection provided data to show that BALB/c mice were able to recruit more leukocytes into the lungs than CBA/Ca mice, following infection. In the lungs, BALB/c mice recruited significantly more neutrophils than CBA/Ca mice at 12 and 24 hours post-infection. Histological studies reflected the cellular recruitment data. Inflammatory lesions in BALB/c mice were visible much earlier than in CBA/Ca mice and there was a greater cellular infiltration into the lung tissue of BALB/c mice, at the earlier time points.;Data presented in this thesis suggest that resistance or susceptibility to intranasal pneumococci may have an association with recruitment and/or function of neutrophils. Continuing analysis will reveal possible additional loci and further define the genes involved in the susceptibility or resistance to pneumcoccal disease.