Sphingomyelinases in a journey to combat arthropod‐borne pathogen transmission

Abstract

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 (IsSMase)-like protein, an ortholog of dermonecrotoxin SMase D found in the venom of Loxosceles spp. of spiders. IsSMase 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. 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 tickborne diseases. Such targets could help with the development of an efficient anti-tick vaccine for preventing the transmission of tick-borne pathogens.

A Brief Overview of the Toxic Sphingomyelinase Ds of Brown Recluse Spider Venom and Other Organisms and Simple Methods To Detect Production of Its Signature Cyclic Ceramide Phosphate

“…In addition to spiders, SMase D/PLDs (and homologous genes/peptides) have been found in many other organisms (Cordes and Binford, 2018), although apparently not (so far) mammals (McDermott et al, 2020). These include bacteria (Flores-Diaz et al, 2016;Mariutti et al, 2017), fungi (Dias-Lopes et al, 2013), and some other arthropods, most notably tick saliva (Alarcon-Chaidez et al, 2009;Rajendran et al, 2021;Regmi et al, 2020) and scorpions (Ben Yekhlef et al, 2020;Borchani et al, 2011). Some of these SMases D/PLDs have been established to have activities similar to the sicariid spiders, but most have not been fully characterized.…”

Tick Saliva and Salivary Glands: What Do We Know So Far on Their Role in Arthropod Blood Feeding and Pathogen Transmission

“…Briefly, as ticks attaches and starts feeding, they secrete salivary molecules in saliva. In addition, ticks also secrete exosomes carrying various components including RNA, protein, peptides and miRNA ( Sultana and Neelakanta, 2020 ; Ahmed et al., 2021 ; Rajendran et al., 2021 ). These exosomes could either fuse with the host cells and release content into the host cell or contents are released as soon as tick exosomes enters the vertebrate host.…”

Alterations in arthropod and neuronal exosomes reduce virus transmission and replication in recipient cells

“…Our findings revealed that tick exosomes are salivary/saliva components and that they do facilitate pathogen transmission to the vertebrate host, suggesting that they are novel means of the dissemination from vector to the vertebrate host [3,24] . Treatment of arthropod/neuronal exosomes with GW4869 (a pharmacological agent that interferes with the production and release of exosomes) inhibits the viral RNA/proteins and also interferes with the transmission of flaviviruses from exosomes to the naïve recipient host cells [2][3][4]25,48,49] . The mechanism(s) of GW4869 affecting viral transmission has not been clearly understood.…”