You are here:
GENETIC BASIS OF MURINE ANTIBACTERIAL DEFENSE TO STREPTOCOCCAL LUNG INFECTION
Citation:
HOLLINGSWORTH, J. W., G. WHITEHEAD, K. BERMAN, E. M. TEKIPPE, M. I. GILMOUR, J. E. LARKIN, J. QUACKENBUSH, AND D. A. SCHWARTZ. GENETIC BASIS OF MURINE ANTIBACTERIAL DEFENSE TO STREPTOCOCCAL LUNG INFECTION. Immunogenetics. Springer, New York, NY, 59(9):713-724, (2007).
Impact/Purpose:
To evaluate the effect of genetic background and toll-like receptor 2 on antibacterial defense to streptococcal infection
Description:
To evaluate the effect of genetic background and toll-like receptor 2 on antibacterial defense to streptococcal infection, eight genetically diverse strains of mice (A/J, DBA/2J, CAST/Ei, FVB/NJ, BALB/cJ, C57BL/6J, 129/SvImJ, and C3H/HeJ) and tlr2-deficient mice (C57BL/6tlr2-/-) were infected with three doses of Streptococcus zooepidemicus (500, 5,000, or 50,000 colony forming units) by oropharyngeal aspiration. There was a range of susceptibility between the strains at each dose and time point (6, 24, and 96 hours). At the lowest dose, the 129/SvImJ and C3H/HeJ strains had significantly higher bacterial counts at all three time points after infection when compared to A/J, DBA/2J, CAST/Ei, FVB/NJ, which were relatively resistant to infection at the low dose of innoculum. At the medium dose, 129/SvImJ and C3H/HeJ strains had higher bacterial counts, while A/J, DBA/2J, and BALB/cJ strains showed reduced streptococcal growth. Following inoculation with the highest dose of Streptococcus, there were minimal differences between strains, suggesting the protective impact of modifier genes can be overcome. TLR2-deficient animals demonstrate increased bacterial load with reduced cytokines after 96 hours when compared to C57BL/6J controls. Overall, we identify late antibacterial defense to be TLR2-dependent, as well as, more generally vulnerable (129/SvlmJ and C3H/HeJ) and resistant (A/J and DBA) mouse strains to Streptococcal lung infection. These results demonstrate innate differences in pulmonary host defense to Streptococcus zooepidemicus are dependent on TLR2 and background strain, which support the role of novel genes in the clearance of bacterial pathogens.
