B cells and antibodies are required for resistance to the parasitic gastrointestinal nematode Trichuris muris
B cells and antibodies are required for resistance to the parasitic gastrointestinal nematode Trichuris muris
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DOI：
10.1128/iai.69.6.3860-3868.2001
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发表时间：
2001-06-01
影响因子：
3.1
通讯作者：
Else, KJ
中科院分区：
文献类型：
--
作者：
Blackwell, NM;Else, KJ
先前使用细胞转移和抗体受体敲除小鼠的研究表明，B细胞和抗体不是毛滴虫感染排出机制的必要组成部分。关于抗体在这种感染模型中的重要性，血清转移实验给出了不同的结果，B细胞在启动或维持t细胞反应中的作用尚未得到解决。我们使用B细胞缺陷的mu MT小鼠来确定B细胞是否在抗t小鼠免疫应答中起作用，与野生型C57BL/6小鼠相比，mu MT小鼠对感染敏感。来自感染mu MT小鼠的抗原再刺激的肠系膜淋巴结细胞仅产生初始水平的Th2相关细胞因子，但γ干扰素水平增加。然而，这些小鼠似乎能够增加Th2依赖性粘膜肥大细胞增多症，尽管与野生型小鼠相比，这种情况明显延迟。小鼠抗T能力在C57BL/6脾B细胞重建后得以恢复，体外Th2细胞因子产生对寄生虫抗原的反应也得以恢复。在感染的前2周用抗白细胞介素-12单克隆抗体治疗mu MT小鼠也恢复了免疫力，这表明mu MT螨可以在t细胞启动时被操纵排出湿ms。此外，用从耐药NIH小鼠血清中纯化的寄生虫特异性免疫球蛋白GI治疗mu MT小鼠可以阻止蠕虫的建立，这表明抗体的重要作用。我们的结果作为一个整体描述了B细胞在抵抗肠道线虫的关键作用的第一个详细报告。
Previous studies using cell transfers and antibody receptor knockout mice have shown that B cells and antibodies are not essential components of the expulsion mechanism in Trichuris muris infections. Serum transfer experiments have given mixed results regarding the importance of antibodies in this infection model, and the role of B cells in initiating or maintaining T-cell responses has not been addressed. We used B-cell-deficient mu MT mice to determine if B cells play a role in anti-T: muris immune responses, In contrast to wild-type C57BL/6 mice, mu MT mice were susceptible to infection. Antigen-restimulated mesenteric lymph node cells from infected mu MT mice produced only naive levels of Th2-assoeiated cytokines but had increased levels of gamma interferon, However, these mice appeared capable of mounting a Th2 dependent mucosal mastocytosis, though this was significantly delayed compared to that seen in wild-type mice. Resistance to T, muris was restored following reconstitution with naive C57BL/6 splenic B cells, as was in vitro Th2 cytokine production in response to parasite antigen. Treatment of mu MT mice with anti-interleukin-12 monoclonal antibody during the first 2 weeks of infection also restored immunity, suggesting that mu MT mite can be manipulated to expel wet-ms at the time of T-cell priming, Additionally, treatment of mu MT mice with parasite-specific immunoglobulin GI purified from the serum of resistant NIH mice prevented worm establishment, suggesting an important role for antibodies. Our results as a whole describe the first detailed report of a critical role for B cells in resistance to an intestinal nematode.