title: Genetic basis of murine antibacterial defense to streptococcal lung infection.
abstract: To evaluate the effect of genetic background 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/6(tlr2-/-)) were infected with three doses of Streptococcus zooepidemicus (500, 5,000, or 50,000 colony-forming units) by alveolar challenge. There was a range of susceptibility between the strains at each dose and time point (6, 24, and 96 h). At the lowest dose, the 129/SvImJ and C3H/HeJ strains had significantly higher bacterial counts at all time points after infection, when compared to A/J, DBA/2J, CAST/Ei, FVB/NJ, which were resistant to infection at the low dose of innoculum. At the medium dose, 129/SvImJ and C3H/HeJ had higher bacterial counts, while A/J, DBA/2J, and BALB/cJ showed reduced streptococcal growth. After the highest dose of Streptococcus, there were minimal differences between strains, suggesting the protective impact of modifier genes can be overcome. TLR2-deficient animals contained increased bacterial load with reduced cytokines after 96 h when compared to C57BL/6J controls suggesting a role of innate immunity in late antibacterial defense. Overall, we identify vulnerable (129/SvlmJ and C3H/HeJ) and resistant (A/J, FVB, and DBA) mouse strains to streptococcal lung infection, which demonstrate divergent genetic expression profiles. These results demonstrate that innate differences in pulmonary host defense to S. zooepidemicus are dependent on host genetic factors.
authors: Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University Medical Center, P.O. Box 3136, Durham, NC 27710, USA. holli017@mc.duke.edu
authors: John W
authors: JW
authors: Hollingsworth
authors: Gregory
authors: G
authors: Whitehead
authors: Katherine Gray
authors: KG
authors: Berman
authors: Erin McElvania
authors: EM
authors: Tekippe
authors: M Ian
authors: MI
authors: Gilmour
authors: Jennie E
authors: JE
authors: Larkin
authors: John
authors: J
authors: Quackenbush
authors: David A
authors: DA
authors: Schwartz
mesh_terms: D000818:Animals; D020022:Genetic Predisposition to Disease; D008171:Lung Diseases / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008815:Mice, Inbred Strains; D020411:Oligonucleotide Array Sequence Analysis; D013045:Species Specificity; D013290:Streptococcal Infections / Q000235:genetics* / Q000382:microbiology; D013291:Streptococcus / Q000502:physiology*; D051195:Toll-Like Receptor 2 / Q000235:genetics
chemical_list: C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2
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