Strongyloides stercoralis: Eosinophil-dependent immune-mediated killing of third stage larvae in BALB/cByJ mice
Strongyloides stercoralis: Eosinophil-dependent immune-mediated killing of third stage larvae in BALB/cByJ mice
复制标题
DOI：
10.1006/expr.1996.0034
复制
发表时间：
1996-04-01
影响因子：
2.1
通讯作者：
Abraham, D
中科院分区：
文献类型：
--
作者：
Rotman, HL;Yutanawiboonchai, W;Abraham, D
当BALB/cByJ小鼠接种粗面类圆线虫感染性第三期幼虫(L3)的疫苗时，无论挑战感染是由系统迁移的L3还是L3植入扩散腔组成，挑战蠕虫的存活率都显着降低。在加强免疫后1周，免疫小鼠扩散腔中唯一数量增加的细胞类型是嗜酸性粒细胞，最大水平的嗜酸性粒细胞与寄生虫的杀灭一致。用单抗处理小鼠以清除IL-5或粒细胞，以评估嗜酸性粒细胞在幼虫杀灭中所起的作用。当激发感染包括在加强免疫3周后给予系统迁移的L3时，处理的动物没有表现出免疫力下降。免疫小鼠的嗜酸性粒细胞数量在加强免疫后3周时下降到对照水平，无论是在扩散室内还是在外周血中，而在加强免疫后1周，它们的数量都上升了。然而，在加强免疫3周后，免疫宿主中的幼虫仍然需要宿主细胞与L3直接接触才能杀死幼虫。免疫后1周和3周，用抗IL-5的单抗或粒细胞的mAb清除嗜酸性粒细胞可显著降低保护性免疫。然而，由于系统迁移的L3在免疫的、去嗜酸性粒细胞的动物中仍然被杀死，其他类型的细胞可能在幼虫的破坏中发挥作用。两种人类嗜酸性粒细胞颗粒产物对宿主适应的L3(+)具有毒性，但对感染的L3没有影响，表明宿主适应的幼虫可能是嗜酸性粒细胞介导的破坏第三期幼虫的靶标。这些发现表明，单抗处理使嗜酸性粒细胞失活，取消了对扩散小室内L3的保护性免疫，少量嗜酸性粒细胞足以通过免疫介导杀死斯特拉氏链球菌L3。(C)1996年学术出版社。
Challenge worm survival was significantly reduced when BALB/cByJ mice were vaccinated against Strongyloides stercoralis infective third stage larvae (L3) regardless of whether the challenge infections consisted of systemically migrating L3 or L3 implanted in diffusion chambers. The only cell type that increased in number in diffusion chambers in immunized mice, 1 week after booster immunizations, was the eosinophil, and maximal levels of eosinophils were coincident with parasite killing. Mice were treated with mAb to eliminate IL-5 or granulocytes to assess the role that eosinophils play in larval killing. Treated animals showed no decrease in immunity when challenge infections consisted of systemically migrating L3 administered 3 weeks after booster immunizations. Eosinophil numbers in immunized mice decreased to control levels when measured 3 weeks post-booster immunization, both in diffusion chambers and in the peripheral blood, whereas they were elevated at 1 week after booster immunizations. Direct contact between host cells and L3 was, however, still required for larval killing in immunized hosts 3 weeks after booster immunizations. Elimination of eosinophils by treatment with mAb to IL-5 or granulocytes significantly reduced protective immunity, when L3 were implanted in diffusion chambers at 1 and 3 weeks post-booster. However, as systemically migrating L3 were still killed in immunized, eosinophil-depleted animals, other cell types may play a role in larval destruction. Two human eosinophil granule products were found to be toxic for host-adapted L3(+), but had no effect on infective L3, indicating that host-adapted larvae are possible targets for eosinophil-mediated destruction of third stage larvae. These findings suggest that inactivation of eosinophils by mAb treatment abolishes protective immunity to L3 contained within diffusion chambers and that small numbers of eosinophils are sufficient for immune-mediated killing of S. stercoralis L3. (C) 1996 Academic Press, Inc.