Sphingomyelinases in a journey to combat arthropod-borne pathogen transmission

FEBS Lett. 2021 Jun;595(12):1622-1638. doi: 10.1002/1873-3468.14103. Epub 2021 May 27.


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 tick-borne diseases. Such targets could help with the development of an efficient anti-tick vaccine for preventing the transmission of tick-borne pathogens.

Keywords: ceramide; exosomes; extracellular vesicles; flaviviruses; sphingomyelin; sphingomyelinases; ticks; transmission.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Arbovirus Infections* / immunology
  • Arbovirus Infections* / prevention & control
  • Arbovirus Infections* / transmission
  • Arboviruses / immunology*
  • Arthropod Proteins / immunology*
  • Humans
  • Immunologic Factors / immunology*
  • Ixodes* / immunology
  • Ixodes* / virology
  • Salivary Glands / immunology
  • Salivary Glands / virology
  • Sphingomyelin Phosphodiesterase / immunology*
  • Th1 Cells / immunology
  • Th2 Cells / immunology


  • Arthropod Proteins
  • Immunologic Factors
  • Sphingomyelin Phosphodiesterase