Aedes aegypti salivary gland extract alleviates acute itching by blocking TRPA1 channels

Abstract

Aedes aegypti (Ae. aegypti) saliva induces a variety of anti-inflammatory and immunomodulatory activities. Interestingly, although it is known that mosquito bites cause allergic reactions in sensitised hosts, the primary exposure of humans to Ae. aegypti does not evoke significant itching. Whether active components in the saliva of Ae. aegypti can counteract the normal itch reaction to injury produced by a histaminergic or non-histaminergic pathway in vertebrate hosts is unknown. This study investigated the effects of Ae. aegypti mosquito salivary gland extract (SGE) on sensitive reactions such as itching and associated skin inflammation. Acute pruritus and plasma extravasation were induced in mice by the intradermal injection of either compound 48/80 (C48/80), the Mas-related G protein-coupled receptor (Mrgpr) agonist chloroquine (CQ), or the transient receptor potential ankyrin 1 (TRPA1) agonist allyl isothiocyanate (AITC). The i.d. co-injection of Ae. aegypti SGE inhibited itching, plasma extravasation, and neutrophil influx evoked by C48/80, but it did not significantly affect mast cell degranulation in situ or in vitro. Additionally, SGE partially reduced CQ- and AITC-induced pruritus in vivo, suggesting that SGE affects pruriceptive nerve firing independently of the histaminergic pathway. Activation of TRPA1 significantly increased intracellular Ca2+ in TRPA-1-transfected HEK293t lineage, which was attenuated by SGE addition. We showed for the first time that Ae. aegypti SGE exerts anti-pruriceptive effects, which are partially regulated by the histamine-independent itch TRPA1 pathway. Thus, SGE may possess bioactive molecules with therapeutic potential for treating nonhistaminergic itch.

Dual role of transient receptor potential ankyrin 1 in respiratory and gastrointestinal physiology: From molecular mechanisms to therapeutic targets

“…Among them, Transient Receptor Potential Ankyrin 1 (TRPA1) holds particular interest owing to its responsiveness to numerous environmental irritants and involvement in pain perception and inflammatory processes ( Meseguer et al, 2014 ; Kadkova et al, 2017 ). TRPA1 is expressed in the nervous system, where it contributes to nociception, itching, and neurogenic inflammation ( Nummenmaa et al, 2020 ; Cerqueira et al, 2023 ; De Logu et al, 2023 ), and in the cardiovascular system, where it plays a role in vascular tone regulation ( Alvarado et al, 2021 ). However, the respiratory and gastrointestinal systems are particularly significant owing to their direct contact with environmental stimuli and their susceptibility to TRPA1-mediated responses ( Kaji et al, 2012 ; Kuwaki and Takahashi, 2023 ) which is comparatively less focused.…”

Aedes aegypti salivary extracts exert immunomodulatory effects onmacrophages, dendritic cells, and T lymphocytes and increase Zikavirus production in vitro.

“…The salivary glands of Ae. aegypti harbor an assortment of bioactive constituents capable of shaping the host's immune responses, thereby orchestrating a complex interplay between the mosquito vector and the host immune system (5,(9)(10)(11)(12). Speci cally, the salivary glands of blood-feeding arthropods secrete over 55 bioactive molecules, encompassing protease inhibitors, serine proteases, nucleotidases, immunomodulatory proteins, and antioxidant agents (3,5).…”