Trichinella spiralis Immunomodulation

An Interactive Multifactorial Process

Dalia S Ashour

Disclosures

Expert Rev Clin Immunol. 2013;9(7):669-675. 

In This Article

Abstract and Introduction

Abstract

Many epidemiological data support the postulate that infection with helminths might provide some protection against allergic and autoimmune diseases. Hence arises the concept that helminths strongly influence the immune system and enable protective pathways against these hyperimmune-associated disorders. This review discusses how Trichinella spiralis can make the immune system smarter in dealing with hyperimmune-associated disorders. T. spiralis possesses the capacity to direct the immune system towards a mixed Th1/Th2 phenotype with predominance of Th2 response, or it may interfere with dendritic cell maturation, induce the alternatively activated macrophages and elicit the regulatory arm of the immune response via Treg or regulatory B cells.

Introduction

In 1989, David P Strachan proposed the so-called 'hygiene hypothesis', according to which the decreased incidence of infections with parasites and bacteria in developed countries may be the underlying cause for immune system deregulation and consequential development of allergic and autoimmune diseases.[1,2] Epidemiological data support the postulate that infection with helminths, whether acute or chronic, might provide some protection against these diseases. Hence arises the concept that helminths strongly influence the immune system and enable protective pathways against these hyperimmune-associated disorders.[3]

Helminths can infect humans for many years and in order to maintain their life cycles, helminths have to modulate the host immune response so that it tolerates the parasite via selective suppression or downregulation of the immune system and initiation of a regulatory environment.[1,4] Over the past two decades, it has become increasingly clear that helminths exert strong immunomodulatory effects in their hosts.[5] One of the most important parasites in this field is Trichinella spiralis.

T. spiralis is a unique parasite in which the adult inhabits the small intestine and the larvae encyst in the muscles of the same host. During the intestinal phase, the immune response is mixed Th1/Th2 with initial predominance of the Th1 response and subsequent predominance of the Th2 response.[6] Once a T. spiralis adult worm occupies a niche within enterocytes of the jejunum, a well-characterized type 2 cytokine response (IL-4, IL-5, IL-9 and IL-10) orchestrated by CD4+ T cells is elicited in the mesenteric lymph nodes, which is subsequently recruited to the gut mucosa.[7,8] Furthermore, the long-lasting infection of muscles with Trichinella reflects successful immunomodulation of the immune response, mainly characterized by a Th2 phenotype.[9] Th2 responses to helminths are generally beneficial for the host by repairing or preventing tissue damage caused by the parasite, provided that this response is well controlled.[10]

Many experimental results have shown that Trichinella spp. infection can ameliorate some immune-mediated diseases (Table 1) such as allergic[11] and autoimmune diseases, for example, Crohn's disease,[12] ulcerative colitis,[13] Type 1 diabetes[14] and autoimmune encephalomyelitis.[15] The interpretation of most of these studies depends on the induced Th2 immune response. Skewing of the immune response by most helminths toward Th2 while blocking Th1 response was suggested to attenuate Th1-driven inflammatory responses in the host.[12,16] However, some of those inflammatory disorders ameliorated by T. spiralis are characterized by enhanced Th2 response, for example, allergic disorders and ulcerative colitis. These findings suggest that modulation of immune responses by helminth infection may not be restricted to skewing the immune response to a type 2 response. This concept highlighted the possible role of other alternative mechanisms through which helminth infections can regulate the host immune response, for example, induction of Treg, regulatory B cells (Breg), alternatively activated macrophages (AAMs) and modulation of dendritic cells (DCs).

This review will provide a framework for a better understanding of the immunomodulatory role played by T. spiralis in order to overcome those hyperinflammatory disorders.

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