Basophils Amplify Type 2 Immune Responses, but Do Not Serve a Protective Role, during Chronic Infection of Mice with the Filarial Nematode Litomosoides sigmodontis
Basophils Amplify Type 2 Immune Responses, but Do Not Serve a Protective Role, during Chronic Infection of Mice with the Filarial Nematode Litomosoides sigmodontis
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DOI：
10.4049/jimmunol.0903864
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发表时间：
2010-12-15
影响因子：
4.4
通讯作者：
Mitre, Edward
中科院分区：
文献类型：
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作者：
Torrero, Marina N.;Huebner, Marc P.;Mitre, Edward
慢性蠕虫感染可诱导2型免疫反应，其特征为嗜酸性粒细胞增多、高水平的IgE和增加T细胞产生2型细胞因子。由于嗜碱性粒细胞在蠕虫感染中是IL-4的重要贡献者，而且嗜碱性粒细胞能够诱导CD4(+)T细胞的Th2分化和B细胞的IgE同型转换，我们推测嗜碱性粒细胞在慢性蠕虫感染中具有放大2型免疫反应的功能。为了验证这一点，我们使用慢性蠕虫感染BALB/c小鼠的丝状Litomosoids sigmodontis丝虫模型来评估嗜碱性细胞功能。时程研究表明，在检测到寄生虫特异性IgE后，乙型钩端螺旋体感染过程中，嗜酸性粒细胞、寄生虫抗原特异性的CD4(+)T细胞产生IL-4和IL-5，以及嗜碱性粒细胞活化和IL-4的产生均在感染过程的晚期(6-8wk)达到高峰。混合性别和单性蠕虫植入实验表明，这些反应的相对较晚的峰值与循环微丝虫的出现无关，但可能是由于最初寄生虫载量较低和/或发育中的蠕虫在胸腔内栖息所致。在乙型钩端螺旋体感染过程中，嗜碱性粒细胞的耗尽导致总免疫球蛋白E、寄生虫特异性IgE、嗜酸性粒细胞和寄生虫抗原驱动的CD4(+)T细胞增殖和IL-4产生显著减少，但不改变总蠕虫数量。这些结果表明，嗜碱性粒细胞增强了2型免疫反应，但在慢性感染丝虫乙型线虫的小鼠中不起到保护作用。《免疫学杂志》，2010,185：7426-7434。
Chronic helminth infections induce a type 2 immune response characterized by eosinophilia, high levels of IgE, and increased T cell production of type 2 cytokines. Because basophils have been shown to be substantial contributors of IL-4 in helminth infections, and because basophils are capable of inducing Th2 differentiation of CD4(+) T cells and IgE isotype switching in B cells, we hypothesized that basophils function to amplify type 2 immune responses in chronic helminth infection. To test this, we evaluated basophil function using the Litomosoides sigmodontis filaria model of chronic helminth infection in BALB/c mice. Time-course studies showed that eosinophilia, parasite Ag-specific CD4(+) T cell production of IL-4 and IL-5 and basophil activation and IL-4 production in response to parasite Ag all peak late (6-8 wk) in the course of L. sigmodontis infection, after parasite-specific IgE has become detectable. Mixed-gender and single-sex worm implantation experiments demonstrated that the relatively late peak of these responses was not dependent on the appearance of circulating microfilariae, but may be due to initial low levels of parasite load and/or habitation of the developing worms in the pleural space. Depletion of basophils throughout the course of L. sigmodontis infection caused significant decreases in total and parasite-specific IgE, eosinophilia, and parasite Ag-driven CD4(+) T cell proliferation and IL-4 production, but did not alter total worm numbers. These results demonstrate that basophils amplify type 2 immune responses, but do not serve a protective role, in chronic infection of mice with the filarial nematode L. sigmodontis. The Journal of Immunology, 2010, 185: 7426-7434.