Caterpillar Venom: A Health Hazard of the 21st Century

Abstract

Caterpillar envenomation is a global health threat in the 21st century. Every direct or indirect contact with the urticating hairs of a caterpillar results in clinical manifestations ranging from local dermatitis symptoms to potentially life-threatening systemic effects. This is mainly due to the action of bioactive components in the venom that interfere with targets in the human body. The problem is that doctors are limited to relieve symptoms, since an effective treatment is still lacking. Only for Lonomia species an effective antivenom does exist. The health and economical damage are an underestimated problem and will be even more of a concern in the future. For some caterpillar species, the venom composition has been the subject of investigation, while for many others it remains unknown. Moreover, the targets involved in the pathophysiology are poorly understood. This review aims to give an overview of the knowledge we have today on the venom composition of different caterpillar species along with their pharmacological targets. Epidemiology, mode of action, clinical time course and treatments are also addressed. Finally, we briefly discuss the future perspectives that may open the doors for future research in the world of caterpillar toxins to find an adequate treatment.

Keywords: antivenom; caterpillar venom; pathophysiology; treatments; venomics.

Figure 1

Representation of different venomous caterpillar species. (A) Leucanella memusae, (B) Megalopyge opercularis, (C) pine processionary caterpillar (Thaumetopoea pityocampa), (D) oak processionary caterpillar (Thaumetopoea processionea).

Figure 2

(A) Caterpillar morphology. (B) Schematic representation of setae/spine copied with permission from [44].

Figure 3

Electrophysiology-based bioassay with a two-electrode voltage clamp technique, as measured in Xenopus laevis oocytes. Shown is a validation trace experiment where a G-protein coupled receptor (GPCR) is coupled to an effector channel, an inward rectifier potassium channel via a G_i/o cascade. Currents were induced by exchanging a control saline low potassium solution (ND96 buffer = blue) with a measuring solution with elevated potassium (HK solution = grey). The trace reveals the agonistic activity of a bioactive component originating from a caterpillar (pink). A synthetic agonist was used as control.

Figure 4

Venom components of different caterpillar species and their role on human body targets in the pathophysiology. Caterpillar venoms contain pharmacologically active components that are able to interfere with targets in the normal human cellular physiology. Some components are responsible for the local effects such as inflammation, erythema, edema, intense itch, tissue damage, pain and may exert an allergic reaction. Others affect the hemostasis by acting on the coagulation cascade or on the fibrinolytic pathway. Venom components colored in green activate a step in the cascade, while the components colored in red are able to inhibit a step. In some cases, this can lead to the development of an acute kidney injury (AKI). The venom-induced AKI cascade in the figure is copied with permission from [50].

Figure 5

In these experiments, Yao et al. (2019) [43] tested the response of the crude L. consocia venom (CV) extract on pain-related ion channels: (A) dorsal root ganglion sodium channel (DRG-Na); (B) dorsal root ganglion potassium channel (DRG-K); (C) dorsal root ganglion calcium channel (DRG-Ca); (D) acid-sensing ion channel 2a (mASIC2a); (E) P2X ligand-gated ion channel 3 (hP2X3); (F) mKCNQ4; (G) transient receptor-potential M8 (mTRPM8); (H) transient receptor-potential vanilloid 2 (mTRPV2) (I) TRPV1. The electrophysiological profiles of L. consocia venom reveals a potent and specificity towards the TRPV1 channel with similar amplitude to the agonist, capsaicin, evoked current (I). No evoked currents were seen for the other channels (A–H). The figure was copied with permission from [43].

Figure 6

The TRPV1 antagonist, capsazepine, could not completely eliminate the paw licking behavior. Paw licking duration was monitored by Yao et al. (2019) [43] using the following experimental conditions. (A) Ten microliters of saline (control), capsazepine (CPZ, 2 mM), capsaicin (Cap, 500 µM), crude venom (100 µg/mL), capsaicin (500 µM)/capsazepine (2 mM) mixture, and crude venom (100 µg/mL)/capsazepine (2 mM) mixture injected into the left hind paw of WT mice. Two-sided t-test: *, p < 0.05; n = 6. (B) Mean durations of paw licking induced by 10 µL of saline (control), capsazepine (2 mM), capsaicin (500 µM), crude venom (100 µg/mL), capsaicin (500 µM)/capsazepine (2 mM) mixture, and crude venom (100 µg/mL)/capsazepine (2 mM) mixture injected into the paw of TRPV1 KO mice. The figure was copied with permission from [43].

Figure 7

One-dimensional electrophoretic profile of (A) Saturniidae and (B) Megalopygidae venom extract under reducing (R) and non-reducing (NR) conditions. Lo A: Lonomia obliqua from Argentina; Lo B: Lonomia obliqua from Brazil; Lm: Leucanella memusae; Pf: Podalia ca. fuscescens; MM: molecular mass markers. The figure was copied from Quintana et al. (2017) [18] with permission from Elsevier.