Dock2基因敲除小鼠在肠道细菌感染中的先天性和适应性免疫缺陷的研究（英文）

Defective innate and adaptive immunity against enteric bacterial infection in Dock2 deficient mice

目的:Dock2是细胞分裂贡献者(Dock)家族的成员之一,能够调节免疫细胞的激活和迁移。我们最近的研究表明,Dock2能保护小鼠免受柠檬酸杆菌(Citrobacter rodentium)感染,并且Dock2调节先天免疫细胞如巨噬细胞和中性粒细胞在感染早期的迁移。然而,Dock2如何调节宿主在C. rodentium感染过程中的适应性免疫反应仍然是未知的。方法:用C. rodentium感染WT、Rag1-/-和Dock2-/-小鼠14天和21天,比较生存率、体重、CFU、组织重量、结肠长度、组织学病变。结果:Dock2-/-小鼠在C. rodentium感染后比WT和Rag1-/-小鼠有更低的存活率和更多的体重损失。尽管Dock2-/-小鼠在第21天与Rag1-/-小鼠有相似的粪便CFU,在感染后第14天和第21天,Dock2-/-小鼠比Rag1-/-小鼠具有更高的组织重量、较短的结肠长度和更严重的组织学损伤。结论:结果表明,Dock2-/-小鼠在整个C. rodentium感染中比Rag1-/-小鼠产生更严重的结肠炎,并且可能在肠道细菌感染中在先天性和适应性免疫方面都有缺陷。

Objective:Dock2 is a member of dedicator of cytokinesis(Dock)family and has been suggested to regulate activation and migration of immune cells.Our recent study shows that Dock2 protects mice from Citrobacter rodentium infection,and Dock2 regulates the migration of innate immune cells such as macrophages and neutrophils during early stage of C.rodentium infection.However,how Dock2 regulates host adaptive immunity during C.rodentium infection remains largely unknown.Methods:WT,Rag1^-/-and Dock2^-/-mice were infected with C.rodentium for 14 or 21 days,and survival rates,body weights,CFU,tissue weights,colon lengths,histological lesions were compared.Results:Dock2^-/-mice had less survival rates,more body weight loss than both WT and Rag1^-/-mice during C.rodentium infection.At day 14 and 21 after infection,Dock2-/-mice had higher tissue weights,shorter colon length and higher histological lesions than Rag1^-/-mice,although Dock2^-/-mice had similar fecal CFU to Rag1^-/-mice at day 21.Conclusions:These results suggest that Dock2^-/-mice developed more severe colitis than Rag1^-/-mice throughout C.rodentium infection and might have defect in both innate and adaptive immunity against enteric bacterial infection.