Sphingomyelinases in a journey to combat arthropod-borne pathogen transmission.

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 SMase (IsSMase)-like protein, an ortholog of dermonecrotoxin Sphingomyelinase D found in the venom of Loxosceles spp. of spiders. IsSMase modulates 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 CXCL12 and IL-8 immune response(s) in human skin to delay wound healing and repair processes. IsSMase 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 us develop an efficient anti-tick vaccine to prevent the transmission of tick-borne pathogens.