Filarial nematode parasites secrete a homologue of the human cytokine macrophage migration inhibitory factor
Filarial nematode parasites secrete a homologue of the human cytokine macrophage migration inhibitory factor
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DOI：
10.1128/iai.66.12.5955-5963.1998
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发表时间：
1998-12-01
影响因子：
3.1
通讯作者：
Scott, AL
中科院分区：
文献类型：
--
作者：
Pastrana, DV;Raghavan, N;Scott, AL
丝状线虫寄生虫在抗寄生虫免疫的背景下建立长期慢性感染，这种免疫强烈偏向于Th2反应。导致这种Th2偏向丝虫抗原的机制尚不清楚，但一种可能性是寄生虫产生具有主动改变其免疫环境能力的分子。在这里，我们报道了人类丝虫病寄生虫分泌一种人类促炎细胞因子巨噬细胞迁移抑制因子（MIF）的同源物，该因子具有改变人类单核细胞/巨噬细胞活性的能力。从马来布鲁氏菌感染期幼虫表达文库中分离得到的cDNA克隆编码了一个12.5 kda的蛋白产物（Bm-MIF），该蛋白产物与人类和小鼠MIF的同源性为42%。MIF同源物也在相关丝虫种班氏乌氏菌和盘尾盘尾虫中表达。成虫和幼虫对Bm-mif进行了转录，该蛋白产物存在于虫体提取物和寄生虫的排泄-分泌产物中。免疫组织细胞化学显示，Bm-MIF定位于皮下/侧索细胞、子宫壁和子宫内发育的幼虫。出乎意料的是，重组Bm-MIF和人MIF对人单核/巨噬细胞的活性是相似的。当与单核/巨噬细胞一起进行细胞迁移实验时，Bm-MIP抑制随机迁移。当远离细胞时，Bm-MIF诱导单核细胞/巨噬细胞迁移增加，这种迁移被中和抗Bm-MIF抗体特异性抑制。Bm-MIF首次证明了蠕虫寄生虫产生细胞因子同源物，这些细胞因子同源物有可能改变宿主的免疫反应，促进寄生虫的存活。
Filarial nematode parasites establish long-term chronic infections in the context of an antiparasite immunity that is strongly biased toward a Th2 response. The mechanisms that lead to this Th2 bias toward filarial antigens are not clear, but one possibility is that the parasites produce molecules that have the capacity to proactively modify their immunological environment. Here we report that filarial parasites of humans secrete a homologue of the human proinflammatory cytokine macrophage migration inhibitory factor (MIF) that has the capability of modifying the activity of human monocytes/macrophages. A cDNA clone isolated from a Brugia malayi infective-stage larva expression library encoded a 12.5-kDa protein product (Bm-MIF) with 42% identity to human and murine MIF. MIF homologues were also found to be expressed in the related filarial species Wuchereria bancrofti and Onchocerca volvulus. Bm-mif was transcribed by adult and larval parasites, and the protein product,vas found in somatic extracts and in the parasite's excretory-secretory products. Immunohistocytochemistry revealed that Bm-MIF was localized to cells of the hypodermis/lateral chord, the uterine wall, and larvae developing in utero. Unexpectedly, the activities of recombinant Bm-MIF and human MIF on human monocytes/macrophages were found to be similar. When placed with monocytes/macrophages in a cell migration assay, Bm-MIP inhibited random migration. When placed away from cells, Bm-MIF induced an increase in monocyte/macrophage migration that was specifically inhibited by neutralizing anti-Bm MIF antibodies. Bm-MIF is the first demonstration that helminth parasites produce cytokine homologues that have the potential to modify host immune responses to promote parasite survival.