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Characterization of Clinical and Immune Response in a Rotavirus Diarrhea Model in Suckling Lewis Rats

机译:乳头刘易斯大鼠轮状病毒腹泻模型的临床和免疫应答特征

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Group A rotaviruses (RVs) are the leading pathogens causing diarrhea in children and animals. The present study was designed to establish an experimental model of RV infection and immune response in suckling rats. Wistar (W) and Lewis (L) suckling rats were inoculated orally with two different doses of a simian RV SA-11 strain. RV infection was evaluated by growth rate and clinical indexes. Virus-shedding and serum anti-RV antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Mucosal interferon-γ (IFNγ), specific splenocyte proliferation, and spleen and intestinal intraepithelial lymphocyte (IEL) phenotype were analyzed. No diarrhea was observed in any inoculated Ws. All Ls developed acute moderate diarrhea, and a high score and incidence of diarrhea were found in rats infected with higher titers of RV. Specific humoral and cell systemic immune response was confirmed by splenocyte proliferation and by the presence of serum anti-RV antibodies. Moreover, RV infection induced changes in IEL composition, which showed an increase in the proportion of innate immune cells with respect to cells involved in acquired immunity. This acute moderate diarrhea process constitutes a good experimental model that also provides some immune biomarkers that may allow establishing modulation by drugs or diet components.Abbreviations: Ab, antibody; DI, diarrhea index; DPI, day postinoculation; HD, high dose; IEL, intraepithelial lymphocyte; L, Lewis; LD, low dose; NK, natural killer; PFU, plaque-forming unit; Ref, reference; RV, rotavirus; W, Wistar
机译:A组轮状病毒(RVs)是导致儿童和动物腹泻的主要病原体。本研究旨在建立一个乳鼠右室感染和免疫反应的实验模型。给Wistar(W)和Lewis(L)哺乳大鼠口服两种不同剂量的猿猴RV SA-11株。通过增长率和临床指标评估RV感染。通过酶联免疫吸附测定(ELISA)测量病毒脱落和血清抗RV抗体。分析了粘膜干扰素-γ(IFNγ),特异性脾细胞增殖以及脾和肠上皮内淋巴细胞(IEL)表型。在任何已接种的Ws中均未观察到腹泻。所有的Ls都发展为急性中度腹泻,在滴度较高的RV感染的大鼠中发现高分和腹泻发生率。脾细胞增殖和血清抗RV抗体的存在证实了特定的体液和细胞全身免疫应答。而且,RV感染引起IEL组成的改变,这表明先天免疫细胞相对于参与获得性免疫的细胞比例增加。这种急性中度腹泻过程构成了良好的实验模型,该模型还提供了一些免疫生物标记,可以通过药物或饮食成分建立调节作用。 DI,腹泻指数; DPI,接种后一日; HD,高剂量; IEL,上皮内淋巴细胞; L,刘易斯; LD,低剂量; NK,自然杀手; PFU,菌斑形成单位;参考,参考; RV,轮状病毒; W,Wistar

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