Orally administered Taenia solium Calreticulin prevents experimental intestinal inflammation and is associated with a type 2 immune response

PLoS One. 2017 Oct 16;12(10):e0186510. doi: 10.1371/journal.pone.0186510. eCollection 2017.

Abstract

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.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology
  • Antigens, Helminth / immunology
  • Calreticulin / administration & dosage*
  • Calreticulin / pharmacology*
  • Colitis / immunology*
  • Colitis / metabolism
  • Colitis / prevention & control*
  • Cytokines / metabolism
  • DNA Damage
  • Disease Models, Animal
  • Immunomodulation / drug effects
  • Intestinal Mucosa / metabolism
  • Intestines / drug effects*
  • Intestines / immunology*
  • Mice
  • Taenia solium / chemistry*

Substances

  • Anti-Inflammatory Agents
  • Antigens, Helminth
  • Calreticulin
  • Cytokines

Grant support

FM and AF received funding from Programa de Apoyo a Proyectos de Investigación e Innovacion Tecnologica (PAPIIT), Direccion General de Asuntos del Personal Academico (DGAPA), Universidad Nacional Autonoma de Mexico. Project No. IN214813. JADG received a post-doctoral fellowship from Direccion General de Asuntos del Personal (DGAPA), Universidad Nacional Autonoma de Mexico. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.