| Title: | Nematode ascarosides attenuate mammalian type 2 inflammatory responses |
| Author(s): | Shinoda K; Choe A; Hirahara K; Kiuchi M; Kokubo K; Ichikawa T; Hoki JS; Suzuki AS; Bose N; Appleton JA; Aroian RV; Schroeder FC; Sternberg PW; Nakayama T; |
| Address: | "Department of Immunology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan. Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125. Japan Agency for Medical Research and Development (AMED)-PRIME, AMED, Chuo-ku, Chiba 260-8670, Japan. Boyce Thompson Institute, Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853. Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan. Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853. Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605. Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125; pws@caltech.edu tnakayama@faculty.chiba-u.jp. Department of Immunology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan; pws@caltech.edu tnakayama@faculty.chiba-u.jp. Japan Agency for Medical Research and Development (AMED)-CREST, AMED, Chuo-ku, Chiba 260-8670, Japan" |
| ISSN/ISBN: | 1091-6490 (Electronic) 0027-8424 (Print) 0027-8424 (Linking) |
| Abstract: | "Mounting evidence suggests that nematode infection can protect against disorders of immune dysregulation. Administration of live parasites or their excretory/secretory (ES) products has shown therapeutic effects across a wide range of animal models for immune disorders, including asthma. Human clinical trials of live parasite ingestion for the treatment of immune disorders have produced promising results, yet concerns persist regarding the ingestion of pathogenic organisms and the immunogenicity of protein components. Despite extensive efforts to define the active components of ES products, no small molecules with immune regulatory activity have been identified from nematodes. Here we show that an evolutionarily conserved family of nematode pheromones called ascarosides strongly modulates the pulmonary immune response and reduces asthma severity in mice. Screening the inhibitory effects of ascarosides produced by animal-parasitic nematodes on the development of asthma in an ovalbumin (OVA) murine model, we found that administration of nanogram quantities of ascr#7 prevented the development of lung eosinophilia, goblet cell metaplasia, and airway hyperreactivity. Ascr#7 suppressed the production of IL-33 from lung epithelial cells and reduced the number of memory-type pathogenic Th2 cells and ILC2s in the lung, both key drivers of the pathology of asthma. Our findings suggest that the mammalian immune system recognizes ascarosides as an evolutionarily conserved molecular signature of parasitic nematodes. The identification of a nematode-produced small molecule underlying the well-documented immunomodulatory effects of ES products may enable the development of treatment strategies for allergic diseases" |
| Keywords: | "Animals Asthma/physiopathology Disease Models, Animal Host-Pathogen Interactions Hypersensitivity/physiopathology Inflammation/chemically induced/*prevention & control Mice Mice, Inbred BALB C Nematoda/*chemistry/pathogenicity Ovalbumin/adverse effects Sm;" |
| Notes: | "MedlineShinoda, Kenta Choe, Andrea Hirahara, Kiyoshi Kiuchi, Masahiro Kokubo, Kota Ichikawa, Tomomi Hoki, Jason S Suzuki, Akane S Bose, Neelanjan Appleton, Judith A Aroian, Raffi V Schroeder, Frank C Sternberg, Paul W Nakayama, Toshinori eng R01 AI056189/AI/NIAID NIH HHS/ R01 AI150866/AI/NIAID NIH HHS/ R35 GM131877/GM/NIGMS NIH HHS/ T32 GM008500/GM/NIGMS NIH HHS/ 2022/02/26 Proc Natl Acad Sci U S A. 2022 Mar 1; 119(9):e2108686119. doi: 10.1073/pnas.2108686119" |
