Dome1-JAK-STAT signaling between parasite and host integrates vector immunity and development.
Vipin S RanaChrysoula KitsouShraboni DuttaMichael H RonzettiMin ZhangQuentin BernardAlexis A SmithJulen Tomás-CortázarXiuli YangMing-Jie WuOleksandra KeppleWeizhong LiJennifer E DwyerJaqueline MatiasBolormaa BaljinnyamJonathan D OliverNallakkandi RajeevanJoao H F PedraSukanya NarasimhanYan WangUlrike G MunderlohErol FikrigAnton SimeonovJuan AnguitaUtpal PalPublished in: Science (New York, N.Y.) (2023)
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.