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Intestinal tête-à-tête: helminths blunt immunity against flaviviruses
- Source :
- Cell Res, Cell
- Publication Year :
- 2021
- Publisher :
- Springer Singapore, 2021.
-
Abstract
- 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, as coinfection in Stat6(−/−) mice rescues mortality, treatment of helminth-free WNV-infected mice with 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.
- Subjects :
- viruses
Biology
CD8-Positive T-Lymphocytes
Severity of Illness Index
Article
Mice
Blunt
Immunity
Helminths
parasitic diseases
Animals
Intestinal Mucosa
Molecular Biology
Strongylida Infections
Neurons
Nematospiroides dubius
Coinfection
Flavivirus
Cell Biology
Virology
Research Highlight
Receptors, Interleukin-4
Intestines
Mice, Inbred C57BL
Disease Models, Animal
Disease Susceptibility
STAT6 Transcription Factor
West Nile virus
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cell Res, Cell
- Accession number :
- edsair.doi.dedup.....bb8de5a1b629e68953e4a211bf43be7b