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

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.

Tick hemocytes have pleiotropic roles in microbial infection and arthropod fitness

“…The immune response against microbial infection has been extensively studied in Dipteran insects, but these species do not fully account for the variation in fundamental processes that exists in arthropods (4)(5)(6)(7)(8)(9)(10)18). In this study, we expand on the previous morphological classification of tick hemocytes.…”

“…The evolution of arthropod immune systems is shaped by the environment, longevity, nutrition, microbial exposure, development, and reproduction (1-3). Yet, our current understanding of immunology is centered around Dipteran insects, which reflects an incomplete depiction of arthropod biological networks existing in nature (4)(5)(6)(7)(8)(9)(10). Divergent signaling modules prevail between Dipterans and other arthropods, highlighting the complex and dynamic features occurring across evolutionarily distant species.…”

“…Some components of the canonical IMD pathway are not observed in arachnids, although this immune pathway remains functional and responsive to microbial infection (4)(5)(6)(7)(8). Another instance is the janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, which in flies is elicited by unpaired cytokine-like molecules (13), whereas in ticks host-derived interferon (IFN)- facilitates Dome1-mediated activation (9,10). This biochemical network enhances tick blood meal acquisition and development while inducing the expression of antimicrobial components (9,10).…”

“…Selective pressure caused by longevity (i.e., two to ten years in certain species), exclusive hematophagy in all life stages, long-term dispersal (adaptation to multiple environments) and exposure to an array of microbes, make ticks distinct from other hematophagous arthropods (17,18). While it is acknowledged that the immune system plays an important role in vector competence, our understanding of the mechanisms by which immune resistance balances microbial infection in ticks remain fragmented (6)(7)(8)(9)(10). 4 Hemocytes are specialized arthropod immune cells that function in both cellular and humoral responses.…”

“…Another instance is the janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, which in flies is elicited by unpaired cytokine-like molecules ( 13 ), whereas in ticks host-derived interferon (IFN)-g facilitates Dome1-mediated activation ( 9, 10 ). This biochemical network enhances tick blood meal acquisition and development while inducing the expression of antimicrobial components ( 9, 10 ). Thus, investigating the plasticity of immune networks in evolutionarily divergent organisms may reveal discrete aspects of arthropod biology.…”