Ten Weeks of Infection with a Tissue-Invasive Helminth Protects against Local Immune Complex-Mediated Inflammation, but Not Cutaneous Type I Hypersensitivity, in Previously Sensitized Mice.
Ten Weeks of Infection with a Tissue-Invasive Helminth Protects against Local Immune Complex-Mediated Inflammation, but Not Cutaneous Type I Hypersensitivity, in Previously Sensitized Mice.
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DOI：
10.4049/jimmunol.1500081
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发表时间：
2015-10-01
期刊：
影响因子：
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通讯作者：
Mitre E
中科院分区：
文献类型：
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作者：
Evans H;Killoran KE;Mitre BK;Morris CP;Kim SY;Mitre E
在这项研究中，我们评估的影响，慢性蠕虫感染过敏性疾病的小鼠先前致敏卵清蛋白（OVA）。感染Litomosoides sigmodontis 10周可降低I型超敏反应的免疫学标志物，包括OVA特异性IgE、嗜碱性粒细胞活化和肥大细胞脱粒。尽管有这些减少，但在皮内OVA激发后对立即临床超敏反应没有保护作用。然而，晚期相耳肿胀，由于III型超敏反应，在慢性感染的动物显着减少。总IgG 2a、OVA特异性IgG 2a和OVA特异性IgG 1的水平在感染环境中降低。这些减少可能是由于抗体催化剂增加，因为ELISPOT测定证明感染动物的抗体产生没有受到抑制。攻击后24小时的耳组织学显示，感染动物的耳中细胞浸润减少，中性粒细胞和巨噬细胞数量显著减少。与此一致，感染动物在激发后耳中具有较少的嗜中性粒细胞特异性趋化因子CXCL-1和CXCL-2。此外，在体外刺激与免疫复合物导致显着减少CXCL-1和CXCL-2生产的嗜酸性粒细胞从慢性感染的小鼠。感染动物的嗜酸性粒细胞上FcγRI的表达也显著降低。这些数据表明，慢性丝虫感染抑制嗜酸性粒细胞抗体介导的激活反应，并有可能被用作治疗预先存在的过敏性疾病。
In this study we evaluated the effect chronic helminth infection has on allergic disease in mice previously sensitized to ovalbumin (OVA). 10 weeks of infection with Litomosoides sigmodontis reduced immunological markers of type I hypersensitivity, including OVA-specific IgE, basophil activation, and mast cell degranulation. Despite these reductions, there was no protection against immediate clinical hypersensitivity following intradermal OVA challenge. However, late phase ear swelling, due to type III hypersensitivity, was significantly reduced in chronically infected animals. Levels of total IgG2a, OVA-specific IgG2a, and OVA-specific IgG1 were reduced in the setting of infection. These reductions were likely due to increased antibody catabolism as ELISPOT assays demonstrated that infected animals do not have suppressed antibody production. Ear histology 24 hours after challenge showed infected animals have reduced cellular infiltration in the ear, with significant decreases in numbers of neutrophils and macrophages. Consistent with this, infected animals had less neutrophil-specific chemokines CXCL-1 and CXCL-2 in the ear following challenge. Additionally, in vitro stimulation with immune-complexes resulted in significantly less CXCL-1 and CXCL-2 production by eosinophils from chronically infected mice. Expression of FcγRI was also significantly reduced on eosinophils from infected animals. These data indicate that chronic filarial infection suppresses eosinophilic responses to antibody-mediated activation and has the potential to be used as a therapeutic for pre-existing hypersensitivity diseases.