Diliani N, Dondji B
Laboratory of Cellular Immunology & Parasitology, Department of Biological Sciences, Central Washington University, Ellensburg, WA, USA.
Parasite Immunol. 2017 Oct;39(10). doi: 10.1111/pim.12459.
Approximately one billion people are currently infected with hookworm. Despite its high prevalence and the concomitant immune suppression seen in infected individuals, little research has been performed on the mechanism of immunosuppression by hookworm. Our study focused on characterizing mechanisms utilized by hookworm to suppress the host immune response. Splenocytes and draining lymph node cells from mice injected with hookworm excretory/secretory (ES) proteins showed decreased proliferation in response to both heterologous and species-specific antigens while also having increased nitric oxide secretion. Analysis by fluorescence-activated cell sorting revealed that mice injected with ES had reduced percentages of CD4 T cells indicating potential effects of ES proteins on lymphocyte homeostasis. Antibody and cytokine response analyses demonstrated that immunization with ES proteins decreased IgG and IgG1 levels, also decreased interleukin (IL-)-4 and increased IL-12 and interferon-gamma (IFN-γ) cytokine production suggesting impairment of B-cell activation and a shift towards a nonhealing IL-12 directed T helper-1 immune response. Together, these data demonstrate for the first time that host immunosuppression by hookworms is orchestrated by ES proteins and provide mechanisms underlying the shift towards a nonhealing Th-1 profile as seen in humans suffering from hookworm infection.
目前约有10亿人感染钩虫。尽管钩虫感染率很高，且感染个体存在免疫抑制现象，但关于钩虫免疫抑制机制的研究却很少。我们的研究重点是确定钩虫用于抑制宿主免疫反应的机制。注射钩虫排泄/分泌（ES）蛋白的小鼠的脾细胞和引流淋巴结细胞对异源和种特异性抗原的增殖反应降低，同时一氧化氮分泌增加。荧光激活细胞分选分析显示，注射ES的小鼠CD4 T细胞百分比降低，表明ES蛋白对淋巴细胞稳态有潜在影响。抗体和细胞因子反应分析表明，用ES蛋白免疫可降低IgG和IgG1水平，也可降低白细胞介素（IL）-4水平，并增加IL-12和干扰素-γ（IFN-γ）细胞因子的产生，提示B细胞活化受损，并向非愈合性IL-12主导的辅助性T细胞1型免疫反应转变。总之，这些数据首次证明钩虫对宿主的免疫抑制是由ES蛋白精心策划的，并提供了在钩虫感染患者中观察到的向非愈合性Th-1型转变的潜在机制。
