Hollingsworth John W, Whitehead Gregory, Berman Katherine Gray, Tekippe Erin McElvania, Gilmour M Ian, Larkin Jennie E, Quackenbush John, Schwartz David A
Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University Medical Center, P.O. Box 3136, Durham, NC 27710, USA.
Immunogenetics. 2007 Sep;59(9):713-24. doi: 10.1007/s00251-007-0242-6. Epub 2007 Aug 14.
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.
为评估遗传背景对链球菌感染抗菌防御的影响，通过肺泡攻毒，用三剂兽疫链球菌（500、5000或50000菌落形成单位）感染了八种遗传背景不同的小鼠品系（A/J、DBA/2J、CAST/Ei、FVB/NJ、BALB/cJ、C57BL/6J、129/SvImJ和C3H/HeJ）以及tlr2基因敲除小鼠（C57BL/6(tlr2-/-)）。在每个剂量和时间点（6、24和96小时），各品系之间存在一定范围的易感性差异。在最低剂量时，与对低剂量接种物具有抗感染能力的A/J、DBA/2J、CAST/Ei、FVB/NJ相比，129/SvImJ和C3H/HeJ品系在感染后的所有时间点细菌计数均显著更高。在中等剂量时，129/SvImJ和C3H/HeJ的细菌计数更高，而A/J、DBA/2J和BALB/cJ的链球菌生长有所减少。在最高剂量的链球菌感染后，各品系之间差异极小，这表明修饰基因的保护作用可以被克服。与C57BL/6J对照相比，tlr2基因敲除动物在96小时后细菌载量增加，细胞因子减少，这表明先天免疫在后期抗菌防御中发挥作用。总体而言，我们确定了对链球菌肺部感染易感（129/SvlmJ和C3H/HeJ）和抗性（A/J、FVB和DBA）的小鼠品系，它们表现出不同的基因表达谱。这些结果表明，肺部宿主对兽疫链球菌防御的先天差异取决于宿主遗传因素。
