Myles Matthew H, Livingston Robert S, Franklin Craig L
Research Animal Diagnostic Laboratory, Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri, USA.
Comp Med. 2004 Oct;54(5):549-57.
Helicobacter rodentium was first recognized as a potential pathogen when it was isolated, along with Helicobacter bilis, from a colony of scid/Trp53 knockout mice with diarrhea. Clinical disease in these mice was more severe than that previously reported in mice infected with H. bilis alone, thus suggesting that H. rodentium contributed to the pathogenesis of enteritis. The purpose of the study reported here was to address two questions: is H. rodentium pathogenic in mice, and when co-infection with a pathogenic helicobacter occurs, does H. rodentium augment disease? To this end, A/JCr and C.B-17/IcrCrl-scidBr mice were inoculated with H. rodentium and/or H. hepaticus. Twelve weeks after inoculation, mice were euthanized. The cecum and liver were evaluated microscopically for evidence of disease. Cecal interferon-inducible protein 10 (IP-10), macrophage inflammatory protein 1alpha (MIP-1alpha), interleukin 10 (IL-10), and interferon gamma (IFN-gamma) mRNA values were measured as an indicator of mucosal immune response. Hepatic lesions were not identified in mice mono-infected with H. rodentium; likewise, cecal lesion scores were not significantly different from those of uninfected controls. With the exception of an increased IL-10 mRNA value in SCID mice, mean immune-related gene expression in H. rodentium mono-infected and uninfected control mice was not significantly different. In contrast, all mice infected with H. hepaticus developed moderate to severe hepatitis, significant increase in cecal lesion scores, and increased immune-related gene expression. The C.B-17/IcrCrl-scidBr mice co-infected with H. hepaticus and H. rodentium had liquid cecal contents and low terminal body weight. Further, compared with mice infected with H. hepaticus alone, co-infection was associated with significant increases of IL-10, MIP-1alpha, and IP-10 mRNA values in C.B-17/IcrCrl-scidBr and IFN-gamma and MIP-1alpha mRNA values in A/JCr mice. These results suggested that H. rodentium alone does not cause hepatitis or enteritis in A/JCr or C.B-17/IcrCrl-scidBr mice; however, co-infection with H. hepaticus and H. rodentium was associated with augmented cecal gene expression and clinical manifestation of disease in immunodeficient mice.
啮齿柠檬酸螺旋杆菌最初被认为是一种潜在病原体，当时它与胆汁螺旋杆菌一起，从一群患有腹泻的重症联合免疫缺陷/Trp53基因敲除小鼠中分离出来。这些小鼠的临床疾病比之前仅感染胆汁螺旋杆菌的小鼠更为严重，因此表明啮齿柠檬酸螺旋杆菌促成了肠炎的发病机制。本文所报道研究的目的是解决两个问题：啮齿柠檬酸螺旋杆菌在小鼠中是否具有致病性，以及当与致病性螺旋杆菌共同感染时，啮齿柠檬酸螺旋杆菌是否会加重疾病？为此，给A/JCr和C.B-17/IcrCrl-scidBr小鼠接种了啮齿柠檬酸螺旋杆菌和/或肝螺旋杆菌。接种12周后，对小鼠实施安乐死。对盲肠和肝脏进行显微镜检查以寻找疾病证据。测量盲肠干扰素诱导蛋白10（IP-10）、巨噬细胞炎性蛋白1α（MIP-1α）、白细胞介素10（IL-10）和干扰素γ（IFN-γ）的mRNA值，作为黏膜免疫反应的指标。在仅感染啮齿柠檬酸螺旋杆菌的小鼠中未发现肝脏病变；同样，盲肠病变评分与未感染对照小鼠的评分无显著差异。除重症联合免疫缺陷小鼠中IL-10 mRNA值升高外，啮齿柠檬酸螺旋杆菌单感染小鼠和未感染对照小鼠的平均免疫相关基因表达无显著差异。相比之下，所有感染肝螺旋杆菌的小鼠均出现中度至重度肝炎、盲肠病变评分显著增加以及免疫相关基因表达增加。同时感染肝螺旋杆菌和啮齿柠檬酸螺旋杆菌的C.B-17/IcrCrl-scidBr小鼠盲肠内容物呈液体状且终末体重较低。此外，与仅感染肝螺旋杆菌的小鼠相比，同时感染在C.B-17/IcrCrl-scidBr小鼠中与IL-10、MIP-1α和IP-10 mRNA值的显著增加相关，在A/JCr小鼠中与IFN-γ和MIP-1α mRNA值的显著增加相关。这些结果表明，单独的啮齿柠檬酸螺旋杆菌不会在A/JCr或C.B-17/IcrCrl-scidBr小鼠中引起肝炎或肠炎；然而，肝螺旋杆菌和啮齿柠檬酸螺旋杆菌的共同感染与免疫缺陷小鼠盲肠基因表达增加和疾病临床表现相关。
