Dome1-JAK-STAT signaling between parasite and host integrates vector immunity and development

Science. 2023 Jan 13;379(6628):eabl3837. doi: 10.1126/science.abl3837. Epub 2023 Jan 13.

Abstract

Ancestral signaling pathways serve critical roles in metazoan development, physiology, and immunity. We report an evolutionary interspecies communication pathway involving a central Ixodes scapularis tick receptor termed Dome1, which acquired a mammalian cytokine receptor motif exhibiting high affinity for interferon-gamma (IFN-γ). Host-derived IFN-γ facilitates Dome1-mediated activation of the Ixodes JAK-STAT pathway. This accelerates tick blood meal acquisition and development while upregulating antimicrobial components. The Dome1-JAK-STAT pathway, which exists in most Ixodid tick genomes, regulates the regeneration and proliferation of gut cells-including stem cells-and dictates metamorphosis through the Hedgehog and Notch-Delta networks, ultimately affecting Ixodes vectorial competence. We highlight the evolutionary dependence of I. scapularis on mammalian hosts through cross-species signaling mechanisms that dually influence arthropod immunity and development.

MeSH terms

  • Animals
  • Interferon-gamma
  • Ixodes* / genetics
  • Janus Kinases / genetics
  • Mammals
  • Parasites*
  • STAT Transcription Factors / genetics
  • Signal Transduction

Substances

  • Janus Kinases
  • STAT Transcription Factors
  • Interferon-gamma