Crude Extracts of Caenorhabditis elegans Suppress Airway Inflammation in a Murine Model of Allergic Asthma

Abstract

Epidemiological studies suggest an inverse relationship between helminth infections and allergic disease, and several helminth-derived products have been shown to suppress allergic responses in animals. This study was undertaken to evaluate the effect of a crude extract of Caenorhabditis elegans on allergic airway inflammation in a murine model of asthma. Allergic airway inflammation was induced in BALB/c mice by sensitization with ovalbumin. The effect of the C. elegans crude extract on the development of asthma and on established asthma was evaluated by analyzing airway hyperresponsiveness, serum antibody titers, lung histology and cell counts and cytokine levels in the bronchoalveolar lavage fluid. The role of IFN-γ in the suppression of asthma by the C. elegans crude extract was investigated in IFN-γ knockout and wild-type mice. When mice were sensitized with ovalbumin together with the crude extract of C. elegans, cellular infiltration into the lung was dramatically reduced in comparison with the ovalbumin-treated group. Treatment of mice with the C. elegans crude extract significantly decreased methacholine-induced airway hyperresponsiveness and the total cell counts and levels of IL-4, IL-5 and IL-13 in the bronchoalveolar lavage fluid but increased the levels of IFN-γ and IL-12. Sensitization with the C. elegans crude extract significantly diminished the IgE and IgG1 responses but provoked elevated IgG2a levels. However, the suppressive effect of the C. elegans crude extract was abolished in IFN-γ knockout mice, and the Th2 responses in these mice were as strong as those in wild-type mice sensitized with ovalbumin. The crude extract of C. elegans also suppressed the airway inflammation associated with established asthma. This study provides new insights into immune modulation by the C. elegans crude extract, which suppressed airway inflammation in mice not only during the development of asthma but also after its establishment by skewing allergen-induced Th2 responses to Th1 responses.

Direct comparison of the dynamics of IL‐25‐ and ‘allergen’‐induced airways inflammation, remodelling and hypersensitivity in a murine asthma model

“…The concentrations of IL‐5, IL‐13, IL‐25, IL‐33, TSLP (thymic stromal lymphopoietin) and eotaxin were measured with commercial ELISA kits (eBioscience, San Diego, CA, USA). Serum total IgE and IgG 1 antibody concentrations were measured by ELISA (eBioscience) as previously described . Serum samples collected on day 0 were used as controls.…”

Preventive and therapeutic effects of Trichinella spiralis adult extracts on allergic inflammation in an experimental asthma mouse model

“…This hypothesis suggests that helminth infection shapes the human immune system to reduce its hypersensitivity to allergens or autoantigens [9, 10]. Many experimental studies have provided support for this hypothesis and demonstrated that the immunomodulatory effects of certain helminths and their secreted proteins alleviated not only parasite-specific inflammatory responses that facilitates parasitism, but also other allergic or autoimmune pathology in animal models such as inflammatory bowel disease (IBD), autoimmune encephalomyelitis, arthritis and allergic asthma [11–16]. Since then, clinical trials of helminthic therapy on autoimmune diseases, including inflammatory bowel disease, rhinitis and multiple sclerosis, have been carried out and some extent of therapeutic efficacy has been observed [17–19].…”

Excretory/Secretory Products from Trichinella spiralis Adult Worms Ameliorate DSS-Induced Colitis in Mice

“…An increasing amount of epidemiological evidence has revealed the inverse association of autoimmune or allergic diseases with helminth infections [5], [6], [7]. Since then, a significant number of experimental studies have provided support for this hypothesis and demonstrated that certain helminths, including Trichinella spiralis , have immunomodulatory effects not only on parasite-induced inflammation but also on other immuno-pathologies, such as allergies and autoimmune diseases [8], [9], [10], [11], [12], [13]. Subsequently, early clinical trials for IBD patients with whipworm Trichuris muris or hookworm Necator americanus infections have demonstrated an amelioration of symptoms with a decreased disease activity [14], [15], [16], [17], [18].…”