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Enteric helminth coinfection enhances host susceptibility to neurotropic flaviviruses via a tuft cell-IL-4 receptor signaling axis.
Desai, Pritesh; Janova, Hana; White, James P; Reynoso, Glennys V; Hickman, Heather D; Baldridge, Megan T; Urban, Joseph F; Stappenbeck, Thaddeus S; Thackray, Larissa B; Diamond, Michael S.
Afiliação
  • Desai P; Department of Medicine, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA.
  • Janova H; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA.
  • White JP; Department of Medicine, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA.
  • Reynoso GV; Viral Immunity and Pathogenesis Unit, Laboratory of Clinical Microbiology and Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Hickman HD; Viral Immunity and Pathogenesis Unit, Laboratory of Clinical Microbiology and Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
  • Baldridge MT; Department of Medicine, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA.
  • Urban JF; US Department of Agriculture, Agricultural Research Services, Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, and Beltsville Agricultural Research Center, Animal Parasitic Diseases Laboratory, Beltsville, MD 20705-2350, USA.
  • Stappenbeck TS; Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH 44195, USA.
  • Thackray LB; Department of Medicine, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA.
  • Diamond MS; Department of Medicine, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine
Cell ; 184(5): 1214-1231.e16, 2021 03 04.
Article em En | MEDLINE | ID: mdl-33636133
Although enteric helminth infections modulate immunity to mucosal pathogens, their effects on systemic microbes remain less established. Here, we observe increased mortality in mice coinfected with the enteric helminth Heligmosomoides polygyrus bakeri (Hpb) and West Nile virus (WNV). This enhanced susceptibility is associated with altered gut morphology and transit, translocation of commensal bacteria, impaired WNV-specific T cell responses, and increased virus infection in the gastrointestinal tract and central nervous system. These outcomes were due to type 2 immune skewing, because coinfection in Stat6-/- mice rescues mortality, treatment of helminth-free WNV-infected mice with interleukin (IL)-4 mirrors coinfection, and IL-4 receptor signaling in intestinal epithelial cells mediates the susceptibility phenotypes. Moreover, tuft cell-deficient mice show improved outcomes with coinfection, whereas treatment of helminth-free mice with tuft cell-derived cytokine IL-25 or ligand succinate worsens WNV disease. Thus, helminth activation of tuft cell-IL-4-receptor circuits in the gut exacerbates infection and disease of a neurotropic flavivirus.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vírus do Nilo Ocidental / Nematospiroides dubius / Transdução de Sinais / Infecções por Strongylida / Coinfecção Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vírus do Nilo Ocidental / Nematospiroides dubius / Transdução de Sinais / Infecções por Strongylida / Coinfecção Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article