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美国当代基因型中的感染:免疫反应。

infections in mice: Immunological responses to contemporary genotypes found in the US.

机构信息

Rickettsial Zoonoses Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Atlanta, United States.

出版信息

Virulence. 2021 Dec;12(1):2461-2473. doi: 10.1080/21505594.2021.1975527.

Abstract

is an obligate intracellular bacterium that causes the human disease Q fever, which can manifest as an acute flu-like illness or a long-term chronic illness, such as endocarditis. Three genotypes (ST8, ST16, and ST20) of are commonly found in the contemporary US and are associated with specific animal hosts. Although all three genotypes have been isolated from humans with Q fever, studies comparing virulence between sequence types have been rare. Here, groups of mice were infected via aerosol inoculation with isolates derived from cow's milk, environmental, animal, and human samples. Mice were monitored for weight loss and blood samples were takenweekly. Animals were euthanized at 2- and 12-weeks post-infection, and bacterial burden was determined for tissues by real-time PCR. The levels of anti-Coxiella antibodies and selected inflammatory cytokines were determined for serum samples. Weight loss and splenomegaly were observed in mice infected with ST20 and ST16 isolates but were absent in the mice infected with ST8 isolates. Bacterial concentrations in the tissues were lower in the ST8 isolates at 2 weeks post-infection relative to all other isolates. ST16 and ST20 isolates induced robust antibody and cytokine responses, while ST8 isolates produced significantly lower anti- titers early in the infection but saw increased titers in some animals several weeks post-infection. The data suggest that the ST8 isolates are less virulent in this mouse model, as they produce less robust antibody responses that are slow to develop, relative to the ST16 and ST20 isolates.

摘要

是一种专性细胞内细菌,可引起人类疾病 Q 热,表现为急性流感样疾病或慢性疾病,如心内膜炎。三种基因型(ST8、ST16 和 ST20)在当代美国很常见,与特定的动物宿主有关。尽管所有三种基因型都已从 Q 热患者中分离出来,但比较序列型之间毒力的研究很少。在这里,通过气溶胶接种用来自牛奶、环境、动物和人类样本的分离物感染组小鼠。监测小鼠体重减轻和每周采集血样。动物在感染后 2 周和 12 周时安乐死,并通过实时 PCR 确定组织中的细菌负荷。血清样本用于测定抗柯克斯体抗体和选定的炎症细胞因子水平。感染 ST20 和 ST16 分离株的小鼠出现体重减轻和脾肿大,但感染 ST8 分离株的小鼠没有。与所有其他分离株相比,ST8 分离株在感染后 2 周时组织中的细菌浓度较低。ST16 和 ST20 分离株诱导了强烈的抗体和细胞因子反应,而 ST8 分离株在感染早期产生的抗-滴度明显较低,但在感染数周后一些动物的滴度增加。数据表明,与 ST16 和 ST20 分离株相比,ST8 分离株在这种小鼠模型中的毒力较低,因为它们产生的抗体反应较弱,且发展缓慢。

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