Interferon-γ plays a critical role in intestinal immunity against Salmonella typhimurium infection
Interferon-γ plays a critical role in intestinal immunity against Salmonella typhimurium infection
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DOI：
10.1046/j.1365-2567.2000.00955.x
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发表时间：
2000-03-01
期刊：
影响因子：
6.4
通讯作者：
Husband, AJ
中科院分区：
文献类型：
--
作者：
Bao, S;Beagley, KW;Husband, AJ
沙门氏菌是食源性感染性腹泻的主要原因，人们对了解沙门氏菌感染的发病机制和疫苗开发有很大的兴趣。潜在的疫苗包括S.鼠伤寒。这种非致死性Aro突变体也可用于研究小鼠模型中的沙门氏菌感染。使用这些Aro突变体在正常和细胞因子基因敲除小鼠中进行的全身感染研究表明，干扰素-γ（IFN-γ）在沙门氏菌感染的解决中起着关键作用。目前的研究已经调查了小鼠经口感染减毒沙门氏菌的结果，因为这种感染途径模拟了人类的自然感染。在IFN-γ基因敲除（IFN-γ（-/-））小鼠中，肠道免疫受损，口服攻击导致2周后播散性败血症。在野生型小鼠中未观察到感染传播。在野生型小鼠中，沙门氏菌攻击后肠道中的CD 4和CD 8细胞数量增加，同时主要组织相容性复合体（MHC）II和血管细胞粘附分子-1（VCAM-1）的表达增加。在IFN γ（-/-）小鼠中未观察到此类变化。口服后的挑战，抗脂多糖（LPS）和抗磷酸胆碱抗体增加了100倍以上的血清和粪便颗粒提取物的IFN γ（-/-）小鼠与野生型小鼠相比。我们的数据表明，IFN-γ的生产是必不可少的肠道沙门氏菌感染的决议，抗体对这一过程的影响不大。
Salmonella bacteria are a major cause of food-borne infectious diarrhoea and there is great interest in understanding the pathogenesis of Salmonella infection and in vaccine development. Potential vaccines include the aromatic mutants of S. typhimurium. Such non-lethal Aro mutants have also been useful for studying Salmonella infections in mouse models. Studies of systemic infection, using these Aro mutants, in both normal and cytokine gene knockout mice, indicate that interferon-gamma (IFN-gamma) plays a key role in the resolution of Salmonella infection. The present studies have investigated the outcome of oral infection in mice with attenuated Salmonella because this infection route mimics natural infection in humans. In IFN-gamma gene knockout (IFN-gamma(-/-)) mice, intestinal immunity was impaired and oral challenge resulted in disseminated septicaemia 2 weeks later. No dissemination of infection was seen in wild-type mice. In wild-type mice, both CD4 and CD8 cell numbers increased in the gut following Salmonella challenge, together with increased expression of major histocompatibility complex (MHC) II and vascular cell adhesion molecule-1 (VCAM-1). No such changes were seen in IFN gamma(-/-) mice. Following oral challenge, antilipopolysaccharide (LPS) and antiphosphoryl choline antibodies increased by more than 100-fold in both serum and faecal pellet extracts of IFN gamma(-/-) mice compared with wild-type mice. Our data show that IFN-gamma production is essential for resolution of enteric Salmonella infection and that antibody has little effect on this process.