Anti-inflammatory Potentials of Excretory/Secretory (ES) and Somatic Products of Marshallagia marshalli on Allergic Airway Inflammation in BALB/c Mice

Background: Inverse relationship between helminths infection and immune-mediated diseases has inspired researchers to investigate therapeutic potential of helminths in allergic asthma. Helminth unique ability to induce immunoregulatory responses has already been documented in several experimental studies. This study was designed to investigate whether excretory/secretory (ES) and somatic products of Marshallagia marshalli modulate the development of ovalbumin-induced airway inflammation in a mouse model. Methods: This study was carried out at the laboratories of Immunology and Parasitology of Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran during spring and summer 2015. Allergic airway inflammation was induced in mice by intraperitoneal (IP) injection with ovalbumin (OVA). The effects of ES and somatic products of M. marshalli were analyzed by inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF), pathological changes and IgE response. Results: Treatment with ES and somatic products of M. marshalli decreased cellular infiltration into BALF when they were administered during sensitization with allergen. Pathological changes were decreased in helminth-treated group, as demonstrated by reduced inflammatory cell infiltration, goblet cell hyperplasia, epithelial lesion and smooth muscle hypertrophy. However, no significant differences were observed in IgE serum levels, cytokines and eosinophil counts between different groups. Conclusion: This study provides new insights into anti-inflammatory effects of ES and somatic products of M. marshalli, during the development of non-eosinophilic model of asthma. Further study is necessary to characterize immunomodulatory molecules derived from M. marshalli as a candidate for the treatment of airway inflammation.

[1]  W. Parker,et al.  Overcoming Evolutionary Mismatch by Self-Treatment with Helminths: Current Practices and Experience , 2015 .

[2]  M. Jordana,et al.  Therapeutic potential of anti-IL-6 therapies for granulocytic airway inflammation in asthma , 2015, Allergy, Asthma & Clinical Immunology.

[3]  R. Grencis Immunity to helminths: resistance, regulation, and susceptibility to gastrointestinal nematodes. , 2015, Annual review of immunology.

[4]  H. Helmby Human helminth therapy to treat inflammatory disorders- where do we stand? , 2015, BMC Immunology.

[5]  S. Hartmann,et al.  Therapeutic potential of larval excretory/secretory proteins of the pig whipworm Trichuris suis in allergic disease , 2014, Allergy.

[6]  K. Bønnelykke,et al.  Immune‐mediated diseases and microbial exposure in early life , 2014, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[7]  J. Dalton,et al.  Secreted Proteins from the Helminth Fasciola hepatica Inhibit the Initiation of Autoreactive T Cell Responses and Prevent Diabetes in the NOD Mouse , 2014, PloS one.

[8]  J. Correale,et al.  Parasite Infections in Multiple Sclerosis Modulate Immune Responses through a Retinoic Acid–Dependent Pathway , 2013, The Journal of Immunology.

[9]  R. Vonderheide,et al.  Multicolor flow cytometric analysis of immune cell subsets in tumor-bearing mice. , 2013, Cold Spring Harbor protocols.

[10]  M. Maleki,et al.  Pathophysiology of Marshallagia marshalli in experimentally infected lambs , 2013, Parasitology.

[11]  M. Oh,et al.  The effect of lipopolysaccharide-contaminated ovalbumin on airway inflammation and remodeling in a chronic murine asthma model , 2013 .

[12]  S. Hanauer,et al.  Randomised clinical trial: the safety and tolerability of Trichuris suis ova in patients with Crohn's disease , 2013, Alimentary pharmacology & therapeutics.

[13]  R. Maizels,et al.  Oesophagostomum dentatum Extract Modulates T Cell-Dependent Immune Responses to Bystander Antigens and Prevents the Development of Allergy in Mice , 2013, PloS one.

[14]  J. Ilonen,et al.  The ‘Hygiene hypothesis’ and the sharp gradient in the incidence of autoimmune and allergic diseases between Russian Karelia and Finland , 2013, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[15]  F. Paul,et al.  Trichuris suis ova in relapsing-remitting multiple sclerosis and clinically isolated syndrome (TRIOMS): study protocol for a randomized controlled trial , 2013, Trials.

[16]  R. Hendriks,et al.  Type 2 Innate Lymphocytes in Allergic Airway Inflammation , 2013, Current Allergy and Asthma Reports.

[17]  A. Loukas,et al.  Hookworm Excretory/Secretory Products Induce Interleukin-4 (IL-4)+ IL-10+ CD4+ T Cell Responses and Suppress Pathology in a Mouse Model of Colitis , 2013, Infection and Immunity.

[18]  J. Fleming Helminth therapy and multiple sclerosis. , 2013, International journal for parasitology.

[19]  A. Cooke,et al.  Helminth mediated modulation of Type 1 diabetes (T1D). , 2013, International journal for parasitology.

[20]  H. Schleibinger,et al.  Maintaining health by balancing microbial exposure and prevention of infection: the hygiene hypothesis versus the hypothesis of early immune challenge. , 2013, The Journal of hospital infection.

[21]  R. Maizels,et al.  Helminth Infections and Host Immune Regulation , 2012, Clinical Microbiology Reviews.

[22]  D. Bleich,et al.  Prevention of type 1 diabetes through infection with an intestinal nematode parasite requires IL-10 in the absence of a Th2-type response , 2012, Mucosal Immunology.

[23]  S. Wenzel Asthma phenotypes: the evolution from clinical to molecular approaches , 2012, Nature Medicine.

[24]  Sung-Tae Hong,et al.  Crude Extracts of Caenorhabditis elegans Suppress Airway Inflammation in a Murine Model of Allergic Asthma , 2012, PloS one.

[25]  R. Maizels,et al.  T cells in helminth infection: the regulators and the regulated. , 2012, Trends in immunology.

[26]  A. Mohammadpour,et al.  Effect of verapamil on bronchial goblet cells of asthma: an experimental study on sensitized animals. , 2012, Pulmonary pharmacology & therapeutics.

[27]  M. Yazdanbakhsh,et al.  Regulatory B-cell induction by helminths: implications for allergic disease. , 2011, The Journal of allergy and clinical immunology.

[28]  Carole Ober,et al.  The genetics of asthma and allergic disease: a 21st century perspective , 2011, Immunological reviews.

[29]  R. Maizels,et al.  Diversity and dialogue in immunity to helminths , 2011, Nature Reviews Immunology.

[30]  R. Van Ree,et al.  A longitudinal study of allergy and intestinal helminth infections in semi urban and rural areas of Flores, Indonesia (ImmunoSPIN Study) , 2011, BMC infectious diseases.

[31]  P. Gergen,et al.  Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. , 2011, The New England journal of medicine.

[32]  A. Isaak,et al.  Probiotic helminth administration in relapsing–remitting multiple sclerosis: a phase 1 study , 2011, Multiple sclerosis.

[33]  H. Chung Asthma in childhood: a complex, heterogeneous disease , 2011, Korean journal of pediatrics.

[34]  C. Lloyd,et al.  Functions of T cells in asthma: more than just TH2 cells , 2010, Nature Reviews Immunology.

[35]  M. Harnett,et al.  Helminth-derived immunomodulators: can understanding the worm produce the pill? , 2010, Nature Reviews Immunology.

[36]  B. Everts,et al.  Chronic Helminth Infections Protect Against Allergic Diseases by Active Regulatory Processes , 2010, Current allergy and asthma reports.

[37]  C. Hawrylowicz,et al.  Regulatory T cells in asthma. , 2009, Immunity.

[38]  A. Loukas,et al.  Therapeutic potential of helminth soluble proteins in TNBS‐induced colitis in mice , 2009, Inflammatory bowel diseases.

[39]  M. Teixeira,et al.  IL-33 Induces Antigen-Specific IL-5+ T Cells and Promotes Allergic-Induced Airway Inflammation Independent of IL-41 , 2008, The Journal of Immunology.

[40]  Philip Smith,et al.  Infection with a Helminth Parasite Prevents Experimental Colitis via a Macrophage-Mediated Mechanism1 , 2007, The Journal of Immunology.

[41]  I. Pavord,et al.  Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma , 2007, Thorax.

[42]  J. Kline,et al.  Intestinal Helminths Protect in a Murine Model of Asthma1 , 2006, The Journal of Immunology.

[43]  Justus G. Müller,et al.  Helminth infection modulates the development of allergen-induced airway inflammation. , 2004, International immunology.

[44]  A. Heck,et al.  Comprehensive Analysis of the Secreted Proteins of the Parasite Haemonchus contortus Reveals Extensive Sequence Variation and Differential Immune Recognition* , 2003, The Journal of Biological Chemistry.

[45]  U. Wahn,et al.  Endotoxins prevent murine IgE production, T(H)2 immune responses, and development of airway eosinophilia but not airway hyperreactivity. , 2002, The Journal of allergy and clinical immunology.

[46]  P. Foster,et al.  A novel T cell-regulated mechanism modulating allergen-induced airways hyperreactivity in BALB/c mice independently of IL-4 and IL-5. , 1998, Journal of immunology.

[47]  R. Bergstrom Prevalence of Marshallagia marshalli (Orlov, 1933) in Wild Ruminants in Wyoming , 1975 .

[48]  M. Washington,et al.  Activation of the Epidermal Growth Factor Receptor in Macrophages Regulates Cytokine Production and Experimental Colitis , 2014 .

[49]  J. T. Nazeer,et al.  Evaluation of the Suppressive Effects of Ascaris Pseudo-Coelomic Fluid (PCF), Fasciola Excretory/Secretory Antigen (FES) and Hydatid Antigen-B (HAgB) on the Development of Experimental Murine Asthma , 2012 .

[50]  S. Bokaie,et al.  Study on the Prevalence, Intensity, Seasonal Dynamics of Abomasal Helminths in Sheep from Different Climatic Zones of Iran , 2011 .