Effect of age on susceptibility to Salmonella Typhimurium infection in C57BL/6 mice.

Effect of age on susceptibility to Salmonella Typhimurium infection in C57BL/6 mice.
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DOI:
10.1099/jmm.0.013250-0
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发表时间:
2009-12
影响因子:
3
通讯作者:
Meydani SN
Meydani SN
中科院分区:
医学3区
文献类型:
--
作者:
Ren Z;Gay R;Thomas A;Pae M;Wu D;Logsdon L;Mecsas J;Meydani SN

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衰老与免疫功能下降有关,这使老年人更容易受到感染。关于与年龄相关的鼠伤寒沙门氏菌(S. Typhimurium)易感性增加机制的信息有限。特别是,人们对免疫反应在这种与年龄相关的差异中的参与知之甚少。我们采用链霉素 (STREP) 预处理的 C57BL/6 小鼠来开发小鼠模型,该模型将证明对鼠伤寒沙门氏菌的敏感性和免疫反应与年龄相关的差异。在该模型中,口服接种 3×108 CFU 或 1 ×106 CFU 剂量的鼠伤寒沙门氏菌的老年小鼠在回肠、结肠、派尔氏集结、脾脏和肝脏中的鼠伤寒沙门氏菌定植量显着高于年轻小鼠。感染后第 1 天和第 2 天,老年小鼠的体重减轻明显高于年轻小鼠。为了应对鼠伤寒沙门氏菌感染,年老小鼠的脾脏和肠系膜淋巴结细胞中 IFN-γ 和 TNF-α 的离体产量未能增加到与年轻小鼠相同的程度,这与它们无法将中性粒细胞和巨噬细胞的存在维持在“年轻”水平有关。这些结果表明,经STREP预处理的C57BL/6老年小鼠比年轻小鼠更容易受到鼠伤寒沙门氏菌感染,这可能是由于与年轻小鼠相比,IFN-γ和TNF-α的产生受损,以及响应鼠伤寒沙门氏菌感染的中性粒细胞和巨噬细胞数量发生相应变化。
Aging is associated with a decline in immune function, which predisposes the elderly to higher incidence of infections. Information on the mechanism of age-related increase in susceptibility to Salmonella enterica serovar Typhimurium (S. Typhimurium) is limited. In particular, little is known regarding the involvement of the immune response in this age-related difference. We employed the streptomycin (STREP)-pretreated C57BL/6 mice to develop a mouse model that would demonstrate age-related difference in susceptibility and immune response to S. Typhimurium. In this model, old mice inoculated orally with 3×108 CFU or 1 ×106 CFU doses of S. Typhimurium had significantly greater S. Typhimurium colonization in ileum, colon, Peyer’s patches, spleen, and liver than those of young mice. Old mice had significantly higher weight loss than young mice on days 1 and 2 postinfection. In response to S. Typhimurium infection, the old mice failed to increase ex vivo production of IFN-γ and TNF-α in spleen and mesenteric lymph node cells to the same degree as those observed in the young mice, which was associated with their inability to maintain the presence of neutrophils and macrophages at a “youthful” level. These results indicate that STREP-pretreated C57BL/6 old mice are more susceptible to S. Typhimurium infection than young mice, which might be due to impaired IFN-γ and TNF-α production as well as the corresponding change in the number of neutrophils and macrophages in response to S. Typhimurium infection compared to young mice.
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