Mendlovic Fela, Cruz-Rivera Mayra, Diaz-Gandarilla Jose Alfredo, Flores-Torres Marco Antonio, Avila Guillermina, Perfiliev Maria, Salazar Ana Maria, Arriaga-Pizano Lourdes, Ostrosky-Wegman Patricia, Flisser Ana
Departamento de Microbiologia y Parasitologia, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Ciudad de Mexico, Mexico.
Facultad de Ciencias de la Salud, Universidad Anahuac Mexico Norte, Huixquilucan, Estado de Mexico, Mexico.
PLoS One. 2017 Oct 16;12(10):e0186510. doi: 10.1371/journal.pone.0186510. eCollection 2017.
Intestinal helminth antigens are inducers of type 2 responses and can elicit regulatory immune responses, resulting in dampened inflammation. Several platyhelminth proteins with anti-inflammatory activity have been reported. We have identified, cloned and expressed the Taenia solium calreticulin (rTsCRT) and shown that it predominantly induces a type 2 response characterized by IgG1, IL-4 and IL-5 production in mice. Here, we report the rTsCRT anti-inflammatory activity in a well-known experimental colitis murine model. Mice were orally immunized with purified rTsCRT and colitis was induced with trinitrobenzene sulfonic acid (TNBS). Clinical signs of disease, macroscopic and microscopic tissue inflammation, cytokine production and micronuclei formation, as a marker of genotoxicity, were measured in order to assess the effect of rTsCRT immunization on experimentally induced colitis. rTsCRT administration prior to TNBS instillation significantly reduced the inflammatory parameters, including the acute phase cytokines TNF-α, IL-1β and IL-6. Dampened inflammation was associated with increased local expression of IL-13 and systemic IL-10 and TGF-β production. Genotoxic damage produced by the inflammatory response was also precluded. Our results show that oral treatment with rTsCRT prevents excessive TNBS-induced inflammation in mice and suggest that rTsCRT has immunomodulatory properties associated with the expression of type 2 and regulatory cytokines commonly observed in other helminths.
肠道蠕虫抗原是2型反应的诱导剂,可引发调节性免疫反应,从而减轻炎症。已经报道了几种具有抗炎活性的扁形虫蛋白。我们已经鉴定、克隆并表达了猪带绦虫钙网蛋白(rTsCRT),并表明它在小鼠中主要诱导以IgG1、IL-4和IL-5产生为特征的2型反应。在此,我们报告rTsCRT在一个著名的实验性结肠炎小鼠模型中的抗炎活性。用纯化的rTsCRT对小鼠进行口服免疫,并用三硝基苯磺酸(TNBS)诱导结肠炎。测量疾病的临床症状、宏观和微观组织炎症、细胞因子产生以及作为遗传毒性标志物的微核形成,以评估rTsCRT免疫对实验性诱导结肠炎的影响。在TNBS注入前给予rTsCRT可显著降低炎症参数,包括急性期细胞因子TNF-α、IL-1β和IL-6。炎症减轻与IL-13局部表达增加以及全身IL-10和TGF-β产生有关。炎症反应产生的遗传毒性损伤也被排除。我们的结果表明,用rTsCRT进行口服治疗可预防小鼠中TNBS诱导的过度炎症,并表明rTsCRT具有与在其他蠕虫中常见的2型和调节性细胞因子表达相关的免疫调节特性。