Immunodeficiency disorders and autoimmune diseases are common, but a lack of effective targeted drugs and the side-effects of existing drugs have stimulated interest in finding therapeutic alternatives. Naturally derived substances are a recognized source of novel drugs, and tick saliva is increasingly recognized as a rich source of bioactive molecules with specific functions. Ticks use their saliva to overcome the innate and adaptive host immune systems. Their saliva is a rich cocktail of molecules including proteins, peptides, lipid derivatives, and recently discovered non-coding RNAs that inhibit or modulate vertebrate immune reactions. A number of tick saliva and/or salivary gland molecules have been characterized and shown to be promising candidates for drug development for vertebrate immune diseases. However, further validation of these molecules at the molecular, cellular, and organism levels is now required to progress lead candidates to clinical testing. In this paper, we review the data on the immuno-pharmacological aspects of tick salivary compounds characterized in vitro and/or in vivo and present recent findings on non-coding RNAs that might be exploitable as immunomodulatory therapies.

Department of Medical Biology Faculty of Science University of South Bohemia in České Budějovice České Budějovice Czechia

Innovation and Development Laboratory Innovation and Development Center Instituto Butantan São Paulo Brazil

Institut Pasteur de Tunis LR19IPTX Service d'Entomologie Médicale Université de Tunis El Manar Tunis Tunisia

Institute of Parasitology Biology Centre Czech Academy of Sciences České Budějovice Czechia

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Bulk and single-nucleus RNA sequencing highlight immune pathways induced in individuals during an Ixodes scapularis tick bite

Protease-bound structure of Ricistatin provides insights into the mechanism of action of tick salivary cystatins in the vertebrate host

Iripin-1, a new anti-inflammatory tick serpin, inhibits leukocyte recruitment in vivo while altering the levels of chemokines and adhesion molecules

Transcriptomic analysis of the tick midgut and salivary gland responses upon repeated blood-feeding on a vertebrate host

Serpins in Tick Physiology and Tick-Host Interaction

Insights into the Role of Tick Salivary Protease Inhibitors during Ectoparasite-Host Crosstalk

Long Non-Coding RNAs and Their Potential Roles in the Vector-Host-Pathogen Triad