Li Erqiu, Zhou Ping, Petrin Ziva, Singer Steven M
Department of Biology, Georgetown University, Washington, DC 20057, USA.
Infect Immun. 2004 Nov;72(11):6642-9. doi: 10.1128/IAI.72.11.6642-6649.2004.
Mast cells are important for protective immunity to intestinal helminth infections and as mediators of allergic disease. Their role in protozoan infections is less well described. We have therefore analyzed mast cell responses and parasite control in mice infected with the protozoan Giardia lamblia. We also measured immunoglobulin A (IgA) responses to the parasite, as IgA can have a protective role in this model. c-kit w/wv mice failed to make parasite-specific IgA, mount a mast cell response, or eliminate the infection. Anti-c-kit-treated C57BL/6 mice had normal IgA responses, lacked mast cell responses, had reduced interleukin-6 (IL-6) mRNA in the small intestine, and failed to control the infection within 10 days. IL-9-deficient mice had a significant but reduced mast cell response and still controlled the infection within 2 weeks. Interestingly, IL-6-deficient mice had enhanced mast cell responses yet failed to rapidly control the infection. However, prevention of mast cell responses in IL-6-deficient mice by anti-c-kit treatment did not lead to parasite elimination. Both IL-6- and IL-9-deficient mice had normal IgA production. IL-6-deficient mice had significant serum levels of mast cell mediators, histamine and mast cell protease 1, following infection. Together, these results show that mast cells are important for the rapid control of Giardia infections in mice. Furthermore, they show that IL-6 is not necessary for these mast cell responses. Instead, they suggest that mast cell production of IL-6 appears to be important for control of this infection.
肥大细胞对于肠道蠕虫感染的保护性免疫以及作为过敏性疾病的介质至关重要。它们在原生动物感染中的作用描述较少。因此，我们分析了感染原生动物贾第虫的小鼠的肥大细胞反应和寄生虫控制情况。我们还测量了对该寄生虫的免疫球蛋白A（IgA）反应，因为IgA在该模型中可能具有保护作用。c-kit w/wv小鼠无法产生寄生虫特异性IgA，无法产生肥大细胞反应，也无法消除感染。用抗c-kit处理的C57BL/6小鼠具有正常的IgA反应，缺乏肥大细胞反应，小肠中白细胞介素-6（IL-6）mRNA减少，并且在10天内无法控制感染。IL-9缺陷小鼠具有显著但减弱的肥大细胞反应，并且在2周内仍能控制感染。有趣的是，IL-6缺陷小鼠的肥大细胞反应增强，但未能迅速控制感染。然而，通过抗c-kit处理在IL-6缺陷小鼠中预防肥大细胞反应并不会导致寄生虫消除。IL-6和IL-9缺陷小鼠均具有正常的IgA产生。感染后，IL-6缺陷小鼠的血清中肥大细胞介质、组胺和肥大细胞蛋白酶1的水平显著升高。总之，这些结果表明肥大细胞对于小鼠中贾第虫感染的快速控制很重要。此外，它们表明IL-6对于这些肥大细胞反应不是必需的。相反，它们表明肥大细胞产生的IL-6似乎对于控制这种感染很重要。
