Sphingomyelinases in a journey to combat arthropod-borne pathogen transmission

[摘要] Ixodes scapularis ticks feed on humans and other vertebrate hosts and transmit several pathogens of public health concern. Tick saliva is a complex mixture of bioactive proteins, lipids and immunomodulators, such as I. scapularis sphingomyelinase ( Is SMase) - like protein, an ortholog of dermonecrotoxin SMase D found in the venom of Loxosceles spp. of spiders. Is SMase modulates the host immune response towards Th2, which suppresses Th1-mediated cytokines to facilitate pathogen transmission. Arboviruses utilize exosomes for their transmission from tick to the vertebrate host, and exosomes derived from tick saliva/salivary glands suppress C-X-C motif chemokine ligand 12 and interleukin-8 immune response(s) in human skin to delay wound healing and repair processes. Is SMase affects also viral replication and exosome biogenesis, thereby inhibiting tick-to-vertebrate host transmission of pathogenic exosomes. In this review, we elaborate on exosomes and their biogenesis as potential candidates for developing novel control measure(s) to combat tick-borne diseases. Such targets could help with the development of an efficient anti-tick vaccine for preventing the transmission of tick-borne pathogens.

[关键词] ceramide;exosomes;extracellular vesicles;flaviviruses;sphingomyelin;sphingomyelinases;ticks;transmission