IgG and IgE Collaboratively Accelerate Expulsion of Strongyloides venezuelensis in a Primary Infection
IgG and IgE Collaboratively Accelerate Expulsion of Strongyloides venezuelensis in a Primary Infection
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DOI：
10.1128/iai.00285-13
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发表时间：
2013-07-01
影响因子：
3.1
通讯作者：
Nakanishi, Kenji
中科院分区：
文献类型：
--
作者：
Matsumoto, Makoto;Sasaki, Yuki;Nakanishi, Kenji
宿主部署免疫反应的子集来驱逐蠕虫，这取决于蠕虫的性质。委内瑞拉圆线虫（Strongyloides venezuelensis）是人类病原体S. Stercoralis自然感染啮齿动物，并已被用作实验模型。在这里，我们表明，免疫球蛋白G（IgG）和IgE的诱导是快速驱逐S的先决条件。委内瑞拉人在初次感染期间。活化诱导的胞苷脱氨酶缺陷（AID（-/-））小鼠缺乏将IgM转化为其他同种型的能力，在感染S.委内瑞拉。尽管AID（-/-）小鼠正常排出巴西日本圆线虫，但它们需要更长的时间才能排出S。venezuelensis小鼠比野生型（WT）小鼠更高。从S. venezuelensis-infected，但不是N.感染巴西链球菌的小鼠恢复了AID（-/-）小鼠迅速排出S.委内瑞拉。免疫血清来源的IgG和IgE分别通过Fc γ受体III（Fc γ RIII）和Fc γ受体I（Fc γ RI）诱导蠕虫排出，IgG和IgE的混合物显示协同作用。而Fc γ RIII-/-小鼠或Fc γ RI α（-/-）小鼠正常情况下可以排出S。委内瑞拉人、Fc γ RIII-/-小鼠（当它们的IgE被抗IgE中和时）或Fc γ RIII α（-/-）小鼠（当它们的IgG与Fc γ RIII的结合被抗Fc γ RIII阻断时）显示出显著降低的排出S.委内瑞拉。这些数据表明，IgG和IgE发挥多余的作用，但一致行动，以加速S。委内瑞拉驱逐肥大细胞缺陷的小鼠，即使是那些具有免疫血清来源的IgG或IgE的小鼠，也不能排出S。提示肥大细胞是IgG和IgE的细胞靶点。
The host deploys a subset of immune responses to expel helminths, which differs depending on the nature of the helminth. Strongyloides venezuelensis, a counterpart of the human pathogen S. stercoralis, naturally infects rodents and has been used as an experimental model. Here we show that induction of immunoglobulin G (IgG) and IgE is a prerequisite for rapid expulsion of S. venezuelensis during a primary infection. Activation-induced cytidine deaminase-deficient (AID(-/-)) mice, which lack the ability to switch IgM to other isotypes, normally developed T-helper 2 (Th2) cells and intestinal mastocytosis after infection with S. venezuelensis. Although AID(-/-) mice expelled Nippostrongylus brasiliensis normally, they required a much longer period to expel S. venezuelensis than wild-type (WT) mice. Adoptive transfers of immune sera from S. venezuelensis-infected but not N. brasiliensis-infected mice restored the ability of AID(-/-) mice to promptly expel S. venezuelensis. Immune serum-derived IgG and IgE induced worm expulsion via Fc gamma receptor III (Fc gamma RIII) and Fc epsilon receptor I (Fc epsilon RI), respectively, and a mixture of IgG and IgE showed collaborative effects. Whereas Fc gamma RIII-/- mice or Fc epsilon RI alpha(-/-) mice normally could expel S. venezuelensis, Fc gamma RIII-/- mice, when their IgE was neutralized by anti-IgE, or Fc epsilon RI alpha(-/-) mice, when their IgG binding to Fc gamma RIII was blocked by anti-Fc gamma RIII, showed a markedly reduced ability to expel S. venezuelensis. These data reveal that IgG and IgE play redundant roles but act in concert to accelerate S. venezuelensis expulsion. Mast cell-deficient mice, even those equipped with immune serum-derived IgG or IgE, failed to expel S. venezuelensis promptly, suggesting that mast cells are cellular targets of IgG and IgE.