Rotman H L, Yutanawiboonchai W, Brigandi R A, Leon O, Gleich G J, Nolan T J, Schad G A, Abraham D
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Exp Parasitol. 1996 Apr;82(3):267-78. doi: 10.1006/expr.1996.0034.
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.
当BALB/cByJ小鼠接种针对粪类圆线虫感染性第三期幼虫(L3)的疫苗时,无论攻击感染是由全身迁移的L3还是植入扩散室的L3组成,攻击蠕虫的存活率都显著降低。在加强免疫1周后,免疫小鼠扩散室中数量增加的唯一细胞类型是嗜酸性粒细胞,嗜酸性粒细胞的最高水平与寄生虫杀伤同时出现。用单克隆抗体处理小鼠以消除IL-5或粒细胞,以评估嗜酸性粒细胞在幼虫杀伤中的作用。当攻击感染由加强免疫3周后全身迁移的L3组成时,处理过的动物免疫力没有下降。在加强免疫后3周测量时,免疫小鼠扩散室和外周血中的嗜酸性粒细胞数量降至对照水平,而在加强免疫后1周时它们升高。然而,在加强免疫3周后的免疫宿主中,幼虫杀伤仍需要宿主细胞与L3直接接触。在用抗IL-5单克隆抗体或粒细胞处理消除嗜酸性粒细胞后,当在加强免疫后1周和3周将L3植入扩散室时,保护性免疫力显著降低。然而,由于全身迁移的L3在免疫的、嗜酸性粒细胞减少的动物中仍被杀死,其他细胞类型可能在幼虫破坏中起作用。发现两种人类嗜酸性粒细胞颗粒产物对宿主适应性L3+有毒,但对感染性L3没有影响,这表明宿主适应性幼虫可能是嗜酸性粒细胞介导的第三期幼虫破坏的靶标。这些发现表明,通过单克隆抗体处理使嗜酸性粒细胞失活会消除对扩散室内L3的保护性免疫,并且少量嗜酸性粒细胞足以进行免疫介导的粪类圆线虫L3杀伤。