The allergic response mediated by fire ant venom proteins

Daniel Zamith-Miranda, Eduardo G. P. Fox, Ana Paula Monteiro, Diogo Gama, Luiz E. Poublan, Almair Ferreira de Araujo, Maria F. C. Araujo, Georgia C. Atella, Ednildo A. Machado, Bruno L. Diaz
2018 Scientific Reports  
Fire ants are widely studied, invasive and venomous arthropod pests. There is significant biomedical interest in immunotherapy against fire ant stings. However, mainly due to practical reasons, the physiological effects of envenomation has remained poorly characterized. The present study takes advantage of a recently-described venom protein extract to delineate the immunological pathways underlying the allergic reaction to fire ant venom toxins. Mice were injected with controlled doses of venom
more » ... lled doses of venom protein extract. Following sensitization and a second exposure, a marked footpad swelling was observed. Based on eosinophil recruitment and production of Th2 cytokines, we hereby establish that fire ant proteins per se can lead to an allergic response, which casts a new light into the mechanism of action of these toxins. The Red Imported Fire Ant (RIFA) Solenopsis invicta Buren (Insecta: Formicidae) is one of the most dangerous invasive pests on a global scale 1,2 . These aggressive ants have been inadvertently shipped from South America to many territories around the world over the last century, and are now causing severe problems in regions as far apart as Vietnam, China, Australia, the United States, and the Galapagos archipelago 1,3 . When disturbed, these ants will viciously defend their nests with a venomous sting which can be particularly dangerous to the children 4 and the elderly 5 . Anaphylactic reactions to fire ant stings are recurrent for a fraction of previously sensitized victims, where systemic hypersensitive reactions can pose life-threatening complications 6,7 . Since the prevalence of sensitized subjects in invaded areas is reportedly relatively high 8 , there is a growing demand for immunotherapy methods in regions recently invaded by RIFA 9,10 . Immediate effects of the stings are mainly caused by a major (>95%) fraction of toxic alkaloids, but the later allergic responses 11,12 are solely ascribed to venom proteins. Nonetheless, in spite of over 40 years of research 13 , the allergic reaction caused by fire ant venom has remained poorly characterized. This is primarily because each ant carries venom proteins that amounts to only 0.1% of total body weight 14,15 , rendering bioassays unfeasible. Fortunately, a simple method enabling the isolation of venom proteins from fire ants in large quantities has been recently devised 14 , enabling a range of biological tests which were previously impossible, such as injecting animal models with venom protein fractions. The network of immune cells and expressed factors involved in an allergic response is complex and context-dependent. We provide a simplified general diagram illustrating the proposed allergic reaction induced by injected venom in Fig. 1 . Allergens upon entering the system are endocytosed and processed by phagocytes (e.g. macrophages, dendritic cells) in order to generate peptides. The physico-chemical properties and enzymatic activity of allergens play a central role in the activation and maturation of dendritic cells, which are fundamental steps for proper antigen presentation and immune response triggering. The dendritic cells subsequently migrate to the nearest draining lymph node to present the generated peptides (antigens) coupled to a major histocompatibility complex class II (MHCII) molecule to naive T lymphocytes 16 . Three signals are required during the antigen presentation in order to induce proper T cell activation: the first is provided by the recognition of the complex MHCII/peptide by the T cell receptor (TCR) present in a naive T lymphocyte. The binding between the phagocyte costimulatory molecules (e.g. CD86) and the CD28 receptor present at the T cell surface provides the second Published: xx xx xxxx OPEN www.nature.com/scientificreports/
doi:10.1038/s41598-018-32327-z fatcat:6pkiwqfuibhibeilgfn3vhtzoe