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Heligmosomoides polygyrus: EAE remission is correlated with different systemic cytokine profiles provoked by L4 and adult nematodes
Authors:Katarzyna Donskow-?ysoniewska  Katarzyna Krawczak  Maria Doligalska
Institution:1. Department of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan;2. Department of Virology, National Institute of Health, Islamabad, Pakistan;1. Department of Immunobiology, University of Arizona, 1656 E. Mabel Street, MRB 218,Tucson, AZ 85718, United States;2. Duke Human Vaccine Institute, 909 S. LaSalle Street, Durham, NC 27710, United States;1. Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia;2. Department of Medical Biology, University of Melbourne, Parkville, 3010, Australia;3. Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University Alpert Medical School, Providence, RI, 02912, USA;4. Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France;5. Assistance Publique des Hôpitaux de Marseille, Hôpital de la Timone, Immunology, Marseille Immunopole, France;6. Innate Pharma, Marseille, France;1. Departamento de Medicina Clínica, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil;2. Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil;3. Department of Neurology & Psychiatry, St. Louis University, St. Louis, MO, USA;1. Centre médical des armées de Clermont-Ferrand, antenne médicale d’Issoire, quartier de Bange, 63500 Issoire, France;2. Service de pathologie infectieuse et tropicale, hôpital d’instruction des armées Laveran, 13013 Marseille, France;3. Service de pathologie infectieuse et tropicale, hôpital d’instruction des armées Bégin, 94160 Saint-Mandé, France;4. Centre d’épidémiologie et de santé publique des armées, GSBDD Marseille, 11, avenue de la Corse, BP 426, 13568 Marseille cedex 02, France;1. Servicio de Otorrinolaringología, Hospital Universitario La Paz, Madrid, Spain;2. Servicio de Medicina Preventiva, Hospital Universitario La Paz, Madrid, Spain
Abstract:Primary exposure of mice to gastrointestinal nematode infection with Heligmosomoides polygyrus reduces inflammation in an experimental model of multiple sclerosis. In this study, we aimed to evaluate the ability of H. polygyrus L4 larvae and adults infection to reduce the symptoms of ongoing experimental autoimmune encephalomyelitis (EAE) in female C57Bl/6 mice. EAE was induced by myelin oligodendrocyte glycoprotein MOGp35–55 and after 21 days mice were orally infected with 200 infective larvae (L3) of H. polygyrus. Reduction in EAE symptoms was observed from 2 days post infection and the symptoms were almost completely inhibited at 6 days post infection. This effect was associated with limited total protein content in the cerebrospinal fluid; CSF, and significant decreased pro-inflammatory IL-12p40 concentration and increased concentration of the regulatory cytokines IL-10, TGF-β and IL-6 in the CSF and in the serum. The reduction of EAE symptoms in the enteral phase was associated with higher IL-12p40 concentration in the CSF and very low concentrations of IL-17A and IL-2 in the serum. The fourth stage of gastrointestinal nematode can reverse systemic inflammation in animal models of multiple sclerosis by reducing IL-12 and promoting regulatory cytokines production. The mechanism induced by adult nematodes which sustained EAE inhibition can be provoked by regulatory mechanism connected with reduce IL-17A concentration.
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