Mukai Kaori, Karasuyama Hajime, Kabashima Kenji, Kubo Masato, Galli Stephen J
Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, California, USA.
Infect Immun. 2017 Apr 21;85(5). doi: 10.1128/IAI.00053-17. Print 2017 May.
There is evidence that mast cells, basophils, and IgE can contribute to immune responses to parasites; however, the relative levels of importance of these effector elements in parasite immunity are not fully understood. Previous work in -deficient and c- mutant mice indicated that interleukin-3 and c-Kit contribute to expulsion of the intestinal nematode during primary infection. Our findings in mast cell-deficient mice and two types of mast cell-deficient mice that have normal c- ("Hello ty" and MasTRECK mice) confirmed prior work in mice that suggested that mast cells play an important role in egg clearance in primary infections. We also assessed a possible contribution of basophils in immune responses to By immunohistochemistry, we found that numbers of basophils and mast cells were markedly increased in the jejunal mucosa during primary infections with Studies in basophil-deficient mice revealed a small but significant contribution of basophils to egg clearance in primary infections. Studies in mice deficient in various components of immune responses showed that CD4 T cells and ILC2 cells, IgG, FcRγ, and, to a lesser extent, IgE and FcεRI contribute to effective immunity in primary infections. These findings support the conclusion that the hierarchy of importance of immune effector mechanisms in primary infection is as follows: CD4 T cells/ILC2 cells, IgG, and FcRγ>mast cells>IgE and FcεRI>basophils. In contrast, in secondary infection, our evidence indicates that the presence of CD4 T cells is of critical importance but mast cells, antibodies, and basophils have few or no nonredundant roles.
有证据表明肥大细胞、嗜碱性粒细胞和IgE可参与对寄生虫的免疫反应;然而,这些效应元件在寄生虫免疫中的相对重要程度尚未完全明确。先前针对白细胞介素-3缺陷和c-Kit突变小鼠的研究表明,白细胞介素-3和c-Kit在初次感染期间有助于排出肠道线虫。我们在肥大细胞缺陷小鼠以及两种c-Kit正常的肥大细胞缺陷小鼠(“Hello ty”小鼠和MasTRECK小鼠)中的研究结果证实了先前在白细胞介素-3缺陷小鼠中的研究,该研究表明肥大细胞在初次感染中对清除虫卵起着重要作用。我们还评估了嗜碱性粒细胞在对该寄生虫免疫反应中的可能作用。通过免疫组织化学,我们发现在初次感染该寄生虫期间,空肠黏膜中的嗜碱性粒细胞和肥大细胞数量显著增加。对嗜碱性粒细胞缺陷小鼠的研究表明,嗜碱性粒细胞在初次感染中对清除虫卵有微小但显著的作用。对缺乏各种免疫反应成分的小鼠的研究表明,CD4 T细胞和ILC2细胞、IgG、FcRγ,以及在较小程度上的IgE和FcεRI有助于初次感染中的有效免疫。这些发现支持以下结论:在初次感染中免疫效应机制的重要性层次如下:CD4 T细胞/ILC2细胞、IgG和FcRγ>肥大细胞>IgE和FcεRI>嗜碱性粒细胞。相比之下,在再次感染中,我们的证据表明CD4 T细胞的存在至关重要,但肥大细胞、抗体和嗜碱性粒细胞几乎没有或没有非冗余作用。