Immunological and toxinological responses to jellyfish stings

Abstract

Just over a century ago, animal responses to injections of jellyfish extracts unveiled the phenomenon of anaphylaxis. Yet, until very recently, understanding of jellyfish sting toxicity has remained limited. Upon contact, jellyfish stinging cells discharge complex venoms, through thousands of barbed tubules, into the skin resulting in painful and, potentially, lethal envenomations. This review examines the immunological and toxinological responses to stings by prominent species of jellyfish including Physalia sp (Portuguese Man-o-War, Blue-bottle), Cubozoan jellyfish including Chironex fleckeri, several Carybdeids including Carybdea arborifera and Alatina moseri, Linuche unguiculta (Thimble jellyfish), a jellyfish responsible for Irukandji syndrome (Carukia barnesi) and Pelagia noctiluca. Jellyfish venoms are composed of potent proteinaceous porins (cellular membrane pore-forming toxins), neurotoxic peptides, bioactive lipids and other small molecules whilst the tubules contain ancient collagens and chitins. We postulate that immunologically, both tubular structural and functional biopolymers as well as venom components can initiate innate, adaptive, as well as immediate and delayed hypersensitivity reactions that may be amenable to topical anti-inflammatory-immunomodifier therapy. The current challenge for immunotoxinologists is to deconstruct the actions of venom components to target therapeutic modalities for sting treatment.

Fig. 1

Taxonomic overview of medically and toxinologically significant jellyfish, placed in the context of the other major Cnidarian classes. This phylum is one of the oldest living animal groups with major classes extant in Precambrian times. Cnidarians are characterised by the presence of radial symmetry, two cell layers (ecto- and endoderm) with a single body cavity. They are primarily predatory organisms possessing cnidae, an intracellular capsule elaborated by the Golgi apparatus. Specialised cnidae (nematoblasts) elaborate a “stinging cell” (nematocyst) for the purposes of defence and capture of prey. It is these nematocysts that contain diverse and potent venoms.

Fig. 2

(A–D) Light microscopic and scanning electron microscopic images of the Hawaiian box jellyfish Carybdea alata tentacles and nematocysts – prototype examples of the venom injection apparatus in the cubozoa. (A) Light micrograph of contracted proximal tentacle of C. alata exhibiting bands of packed nematocysts in the tentacle tissue. (B) Light micrograph of higher magnification of nematocyst band showing the orientation of undischarged nematocysts in rows. Inset shows the predominant nematocyst type (heterotrichous microbasic euryteles) found in the tentacles of adult C. alata. (C) Low-magnification scanning electron micrograph of distal C. alata tentacle. Discharged heterotrichous microbasic eurytele tubules are evident in raised bands on the outer surface of the tentacle (arrow). (D) High-magnification scanning electron micrograph of C. alata tentacle surface exhibiting discharged heterotrichous microbasic euryteles. Bars 1.5 μm (A), 65 μm (B), 15 μm (B, inset), 400 μm (C), 10 μm (D).

Fig. 3

Schematic representation of the immunological and toxic responses to nematocyst penetration of the skin. Thousands of nematocyst tubules (~1 × 250 microns) covered with mineralized chitinous spines perforate and are left embedded in the skin. Rapid/sustained release of venom into skin: Specific venom porin proteins, peptides, lipids and small molecules activate keritinocytes, dermal mast cells and nocioceptors in skin (including TRPV1 receptors). Venom-activated mast cells explosively degranulate to release factors which elicit rapid immune cell recruitment (extravasation) to the dermal site with resultant swelling, pain and redness. Venom porins, secretagogues, and small molecules directly activate various extravasated immunocytes further initiating inflammatory cytokine responses as well as probable effects secondary to toxin-induced cell damage through the dendritic cell activating necrosis receptors. Chitinous spines and tubule collagen induce sustained activation of innate immunological activation of pro-inflammatory cells, Langerhans dendritic cells, macrophages and mast cells.

Fig. 4

(A, B) Examples of the acute and delayed effects of jellyfish stings on skin. (A) This photographs shows the more delayed effects of a severe chirodropid sting to a child in Thailand. It was taken nine days after the sting and show multiple areas of skin necrosis as well as delayed erythematous urticarial reactions. (B) This photograph shows the acute effects (minutes) of a Blue bottle, Physalia utriculus, sting on a young adult in Australia (Courtesy of Stephen Leahy). Photograph courtesy of Andrew Jones.