Jiménez Juan Carlos, Fontaine Josette, Grzych Jean-Marie, Dei-Cas Eduardo, Capron Monique
INSERM U547, Schistosomiasis, Malaria, and Inflammation, Lille Pasteur Institute (IFR-17), 59019 Lille, France.
Clin Diagn Lab Immunol. 2004 Jan;11(1):152-60. doi: 10.1128/cdli.11.1.152-160.2004.
Giardia, a flagellated protozoan that infects the upper small intestine of its vertebrate host, is the most common parasitic protist responsible for diarrhea worldwide. Molecules released by the parasite, particularly excretory and secretory antigens, seemed to be associated with pathogenesis as well as with the expression of Giardia virulence. In the present work, we examined the effect of oral administration of Giardia intestinalis excretory and secretory antigens on systemic and local antibody response as well as on mucosal injuries in BALB/c mice. Significant titers of serum-specific immunoglobulin G1 (IgG1) and specific IgG2a were observed. Systemic and mucosal specific IgA antibodies were also recorded. A transient production of serum-specific IgE antibody and high total IgE levels were also detected, suggesting the presence in excretory and secretory proteins of factors promoting a specific IgE response. The sera of excretory and secretory antigen-treated mice recognized proteins of 50 and 58 kDa as well as electrophoretic bands of 15, 63, and 72 kDa that could support a proteinase activity. The in vitro exposure of G. intestinalis trophozoites to heat-inactivated sera from mice orally inoculated with excretory and secretory antigens induced a decrease of growth, revealing a complement-independent inhibitory activity of specific serum antibodies. Furthermore, histological evaluation performed on the small and large intestines revealed moderate to acute histological changes comparable to those observed in natural or experimental Giardia infection characterized by eosinophilic infiltration, hypercellularity, and enterocytic desquamation. The present results suggested that Giardia excretory and secretory antigens stimulate a preferential Th2 response, which is probably involved in the intestinal alterations associated with giardiasis.
贾第虫是一种鞭毛虫原生动物,可感染其脊椎动物宿主的上段小肠,是全球范围内导致腹泻的最常见寄生原生生物。该寄生虫释放的分子,特别是排泄和分泌抗原,似乎与发病机制以及贾第虫毒力的表达有关。在本研究中,我们检测了口服肠贾第虫排泄和分泌抗原对BALB/c小鼠全身和局部抗体反应以及对粘膜损伤的影响。观察到血清特异性免疫球蛋白G1(IgG1)和特异性IgG2a的显著滴度。还记录到了全身和粘膜特异性IgA抗体。还检测到血清特异性IgE抗体的短暂产生和高总IgE水平,表明排泄和分泌蛋白中存在促进特异性IgE反应的因子。经排泄和分泌抗原处理的小鼠血清识别出50和58 kDa的蛋白质以及15、63和72 kDa的电泳条带,这些条带可能支持蛋白酶活性。将肠贾第虫滋养体体外暴露于经口服接种排泄和分泌抗原的小鼠的热灭活血清中,可导致生长减少,这表明特异性血清抗体具有不依赖补体的抑制活性。此外,对小肠和大肠进行的组织学评估显示,存在中度至急性组织学变化,类似于在自然或实验性贾第虫感染中观察到的变化,其特征为嗜酸性粒细胞浸润、细胞增多和肠上皮细胞脱落。目前的结果表明贾第虫排泄和分泌抗原刺激优先的Th2反应,这可能与贾第虫病相关的肠道改变有关。