Exploring oak processionary caterpillar induced lepidopterism (part 2): ex vivo bio-assays unmask the role of TRPV1.

As human skin comes into contact with the tiny hairs or setae of the oak processionary caterpillar, Thaumetopoea processionea, a silent yet intense chemical confrontation occurs. The result is a mix of issues: skin rashes and an intense itching that typically lasts days and weeks after the contact. This discomfort poses a significant health threat not only to humans but also to animals. In Western Europe, the alarming increase in outbreaks extends beyond areas near infested trees due to the dispersion of the setae. Predictions indicate a sustained rise in outbreaks, fueled by global changes favoring the caterpillar's survival and distribution. Currently, the absence of an efficient treatment persists due to significant gaps in our comprehension of the pathophysiology associated with this envenomation. Here, we explored the interaction between the venom extract derived from the setae of T. processionea and voltage- and ligand-gated ion channels and receptors. By conducting electrophysiological analyses, we discovered ex vivo evidence highlighting the significant role of TPTX1-Tp1, a peptide toxin from T. processionea, in modulating TRPV1. TPTX1-Tp1 is a secapin-like peptide and demonstrates a unique ability to modulate TRPV1 channels in the presence of capsaicin, leading to cell depolarization, itch and inflammatory responses. This discovery opens new avenues for developing a topical medication, suggesting the incorporation of a TRPV1 blocker as a potential solution for the local effects caused by T. processionea.

Exploring oak processionary caterpillar induced lepidopterism (Part 1): unveiling molecular insights through transcriptomics and proteomics.

Lepidopterism, a skin inflammation condition caused by direct or airborne exposure to irritating hairs (setae) from processionary caterpillars, is becoming a significant public health concern. Recent outbreaks of the oak processionary caterpillar (Thaumetopoea processionea) have caused noteworthy health and economic consequences, with a rising frequency expected in the future, exacerbated by global warming promoting the survival of the caterpillar. Current medical treatments focus on symptom relief due to the lack of an effective therapy. While the source is known, understanding the precise causes of symptoms remain incomplete understood. In this study, we employed an advanced method to extract venom from the setae and identify the venom components through high-quality de novo transcriptomics, venom proteomics, and bioinformatic analysis. A total of 171 venom components were identified, including allergens, odorant binding proteins, small peptides, enzymes, enzyme inhibitors, and chitin biosynthesis products, potentially responsible for inflammatory and allergic reactions. This work presents the first comprehensive proteotranscriptomic database of T. processionea, contributing to understanding the complexity of lepidopterism. Furthermore, these findings hold promise for advancing therapeutic approaches to mitigate the global health impact of T. processionea and related caterpillars.

Histamine Receptors: Ex Vivo Functional Studies Enabling the Discovery of Hits and Pathways.

Histamine receptors (HRs) are G-protein-coupled receptors involved in diverse responses triggered by histamine release during inflammation or by encounters with venomous creatures. Four histamine receptors (H1R-H4R) have been cloned and extensively characterized. These receptors are distributed throughout the body and their activation is associated with clinical manifestations such as urticaria (H1R), gastric acid stimulation (H2R), regulation of neurotransmitters in neuronal diseases (H3R), and immune responses (H4R). Despite significant homologous overlap between H3R and H4R, much remains unknown about their precise roles. Even though some drugs have been developed for H1R, H2R, and H3R, not a single H4R antagonist has been approved for clinical use. To enhance our understanding and advance innovative therapeutic targeting of H1R, H2R, H3R, and H4R, we established a robust ex vivo functional platform. This platform features the successful heterologous expression of H1R-H4R in Xenopus laevis oocytes, utilizing an electrophysiological readout. Our findings contribute to a deeper understanding of the function and pharmacological properties of the histamine receptors. Researchers can benefit from the utility of this platform when investigating the effects of histamine receptors and exploring potential therapeutic targets. In doing so, it broadens the horizon of drug discovery, offering new perspectives for therapeutic interventions.