Zhou P, Li E, Shea-Donohue T, Singer S M
Department of Biology, Georgetown University, Washington, DC 20057, USA.
Parasite Immunol. 2007 Jul;29(7):367-74. doi: 10.1111/j.1365-3024.2007.00953.x.
Giardia lamblia is a ubiquitous parasite that causes diarrhoea. Effective control of Giardia infections in mice has been shown to involve IgA, T cells, mast cells and IL-6. We now show that Tumour necrosis factor alpha (TNFalpha) also plays an important role in the early control of giardiasis. Mice treated with neutralizing anti-TNFalpha antibodies or genetically deficient in TNFalpha were infected with the G. lamblia clone GS/(M)-H7. In both cases, mice lacking TNFalpha had much higher parasite numbers than controls during the first 2 weeks of infections. However, anti-parasite IgA levels, mast cell responses, and IL-4 and IL-6 mRNA levels do not appear significantly altered in the absence of TNFalpha. In addition, we show that mice infected with G. lamblia exhibit increased intestinal permeability, similar to human Giardia infection, and that this increase occurs in both wild-type and TNFalpha deficient mice. We conclude that TNFalpha is essential for host resistance to G. lamblia infection, and that it does not exert its effects through mechanisms previously implicated in control of this parasite.
蓝氏贾第鞭毛虫是一种引起腹泻的常见寄生虫。已证明对小鼠贾第虫感染的有效控制涉及IgA、T细胞、肥大细胞和白细胞介素-6。我们现在表明，肿瘤坏死因子α（TNFα）在贾第虫病的早期控制中也起着重要作用。用中和抗TNFα抗体处理或TNFα基因缺陷的小鼠感染了蓝氏贾第鞭毛虫克隆GS/(M)-H7。在这两种情况下，缺乏TNFα的小鼠在感染的前两周寄生虫数量比对照组高得多。然而，在缺乏TNFα的情况下，抗寄生虫IgA水平、肥大细胞反应以及白细胞介素-4和白细胞介素-6 mRNA水平似乎没有明显改变。此外，我们表明，感染蓝氏贾第鞭毛虫的小鼠表现出肠道通透性增加，类似于人类贾第虫感染，并且这种增加在野生型和TNFα缺陷小鼠中均会发生。我们得出结论，TNFα对于宿主抵抗蓝氏贾第鞭毛虫感染至关重要，并且它不是通过先前涉及控制这种寄生虫的机制发挥作用的。
