Tick salivary protein Cystatin: structure, anti-inflammation and molecular mechanism
- PMID: 38070274
- DOI: 10.1016/j.ttbdis.2023.102289
Tick salivary protein Cystatin: structure, anti-inflammation and molecular mechanism
Abstract
Ticks are blood-sucking ectoparasites that secrete immunomodulatory substances in saliva to hosts during engorging. Cystatins, a tick salivary protein and natural inhibitor of Cathepsins, are attracting growing interest globally because of the immunosuppressive activities and the feasibility as an antigen for developing anti-tick vaccines. This review outlines the classification and the structure of tick Cystatins, and focuses on the anti-inflammatory effects and molecular mechanisms. Tick Cystatins can be divided into four families based on structures and cystatin 1 and cystatin 2 are the most abundant. They are injected into hosts during blood feeding and effectively mitigate the host inflammatory response. Mechanically, tick Cystatins exert anti-inflammatory properties through the inhibition of TLR-NF-κb, JAK-STAT and p38 MAPK signaling pathways. Further investigations are crucial to confirm the reduction of inflammation in other cell types like neutrophils and mast cells, and fully elucidate the underlying mechanism (like the structural mechanism) to make Cystatin a potential candidate for the development of novel anti-inflammation agents.
Keywords: Cystatin; Inflammation; JAK-STAT; MAPK; NF-κb; Tick salivary proteins.
Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.
Similar articles
-
The role of cystatins in tick physiology and blood feeding.Ticks Tick Borne Dis. 2012 Jun;3(3):117-27. doi: 10.1016/j.ttbdis.2012.03.004. Epub 2012 Apr 20. Ticks Tick Borne Dis. 2012. PMID: 22647711 Free PMC article. Review.
-
RNAi-mediated gene silencing to assess the role of synaptobrevin and cystatin in tick blood feeding.Biochem Biophys Res Commun. 2005 Sep 9;334(4):1336-42. doi: 10.1016/j.bbrc.2005.07.036. Biochem Biophys Res Commun. 2005. PMID: 16040003
-
Protease-bound structure of Ricistatin provides insights into the mechanism of action of tick salivary cystatins in the vertebrate host.Cell Mol Life Sci. 2023 Oct 28;80(11):339. doi: 10.1007/s00018-023-04993-4. Cell Mol Life Sci. 2023. PMID: 37898573 Free PMC article.
-
Salivary Tick Cystatin OmC2 Targets Lysosomal Cathepsins S and C in Human Dendritic Cells.Front Cell Infect Microbiol. 2017 Jun 30;7:288. doi: 10.3389/fcimb.2017.00288. eCollection 2017. Front Cell Infect Microbiol. 2017. PMID: 28713775 Free PMC article.
-
Small protease inhibitors in tick saliva and salivary glands and their role in tick-host-pathogen interactions.Biochim Biophys Acta Proteins Proteom. 2020 Feb;1868(2):140336. doi: 10.1016/j.bbapap.2019.140336. Epub 2019 Dec 7. Biochim Biophys Acta Proteins Proteom. 2020. PMID: 31816416 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
