Antibodies and IL-3 support helminth-induced basophil expansion
Antibodies and IL-3 support helminth-induced basophil expansion
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DOI：
10.1073/pnas.1117584109
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发表时间：
2012-09-11
影响因子：
11.1
通讯作者：
Harris, Nicola L.
中科院分区：
文献类型：
--
作者：
Herbst, Tina;Esser, Julia;Harris, Nicola L.
嗜碱性粒细胞是Th 2免疫的强有力介质，并且在过敏性炎症和蠕虫感染期间以增加的数量存在。尽管它们能够增强Th 2免疫，但调节嗜碱性粒细胞发育的机制在很大程度上仍然未知。我们发现同种型转换抗体在促进蠕虫诱导的嗜碱性粒细胞产生后感染Heligmosomoides polygyrus bakeri或Nippostrongylus brasiliensis小鼠的独特作用。H.发现多脑回Bakeri诱导的嗜碱性粒细胞扩增发生在骨髓中，并且在较小程度上发生在脾脏中，并且是IL-3依赖性的。IL-3主要由CD 4（+）CD 49 b（+）NK1.1（-）效应T细胞在这些位点产生，并且需要IL-4 R α链。然而，尽管T细胞IL-3产生完整，但抗体缺陷小鼠表现出有缺陷的嗜碱性粒细胞动员，并且补充免疫血清可独立于所需的IL-4 R α信号传导促进嗜碱性粒细胞。蠕虫诱导的嗜酸性粒细胞增多症不受同种型转换抗体缺乏的影响，这表明对嗜碱性粒细胞的直接影响，而不是通过引发Th 2反应。尽管初次感染H.巴氏多回，攻击感染后的寄生虫排斥反应受到损害。这些数据揭示了同种型转换抗体在蠕虫感染后促进嗜碱性粒细胞扩增和效应子功能中的作用。
Basophils are powerful mediators of Th2 immunity and are present in increased numbers during allergic inflammation and helminth infection. Despite their ability to potentiate Th2 immunity the mechanisms regulating basophil development remain largely unknown. We have found a unique role for isotype-switched antibodies in promoting helminth-induced basophil production following infection of mice with Heligmosomoides polygyrus bakeri or Nippostrongylus brasiliensis. H. polygyrus bakeri-induced basophil expansion was found to occur within the bone marrow, and to a lesser extent the spleen, and was IL-3 dependent. IL-3 was largely produced by CD4(+)CD49b(+)NK1.1(-) effector T cells at these sites, and required the IL-4R alpha chain. However, antibody-deficient mice exhibited defective basophil mobilization despite intact T-cell IL-3 production, and supplementation of mice with immune serum could promote basophilia independently of required IL-4R alpha signaling. Helminth-induced eosinophilia was not affected by the deficiency in isotype-switched antibodies, suggesting a direct effect on basophils rather than through priming of Th2 responses. Although normal type 2 immunity occurred in the basopenic mice following primary infection with H. polygyrus bakeri, parasite rejection following challenge infection was impaired. These data reveal a role for isotype-switched antibodies in promoting basophil expansion and effector function following helminth infection.