Efeitos do alérgeno rPoly p 5 do veneno de P. paulista (Hymenoptera, Vespidae) sobre a resposta inflamatória em macrófagos diferenciados de células da medula óssea
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Data
2021-08-05
Autores
Assugeni, Isabela Oliveira Sandrini [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
Polybia paulista (Hymenoptera, Vespidae) é uma vespa social abundante no sul e sudeste brasileiro, bem como em outros países como Argentina e Paraguai. Esta espécie faz parte das muitas espécies de insetos da ordem Hymenoptera de importância médica. Há um elevado risco de acidentes com ferroadas, sendo que, dependo da quantidade de veneno e do grau de sensibilização do indivíduo, estes acidentes podem acarretar reações alérgicas sistêmicas com chance de evoluírem para o choque anafilático. Estudos com os alérgenos componentes deste veneno têm ganhado crescente interesse devido a resultados promissores de seu uso em diagnóstico laboratorial, bem como em protocolos clínicos de imunoterapia alérgeno específica. Dentre os componentes presentes no veneno de P. paulista, a proteína antígeno 5 (Poly p 5) tem sido considerada um dos principais alérgenos presentes nessa espécie. Todavia, são necessários estudos para esclarecer o papel biológico e funcional deste antígeno no contexto das reações de hipersensibilidade ao veneno. Assim, neste trabalho avaliamos o potencial efeito imunomodulador do alérgeno Antígeno 5 de P. paulista, expresso na forma recombinante (rPoly p 5) em levedura Komagataella phaffi, sobre macrófagos diferenciados de células precursoras, presentes na medula óssea de camundongos (BM-M), ativados e não ativados com estímulos pró-inflamatórios. Para isto foram analisadas, nestas células, alterações de viabilidade celular, capacidade fagocítica, produção de óxido nítrico (NO) e de citocinas pró-inflamatórias, além da expressão das moléculas coestimuladoras CD80 e CD86. Os resultados obtidos, indicam que rPoly p 5 não afeta significativamente a produção de NO em BM-M ativados ou não com estímulos pró-inflamatórios. Todavia, provocou redução na frequência de células expressando as moléculas coestimuladoras CD86 e CD80 em BM-M ativados e não ativados com estímulos próinflamatórios, respectivamente. Adicionalmente, rPoly p 5 induziu ao aumento de IL- 23 e IL-27 em BM-M não ativados e de GM-CSF em BM-M ativados, além de redução de MCP-1 em BM-M ativados. Estes achados podem indicar um papel importante deste alérgeno na polarização de fenótipos funcionais de macrófagos em diferentes estímulos, ativados e não ativados. Neste sentido, a partir das análises das respostas de BM-M quanto ao potencial pró ou anti-inflamatório do rPoly p 5, conclui-se que os resultados aqui obtidos poderão auxiliar na compreensão do potencial imunomodulador dessa proteína na imunidade inata.
Polybia paulista (Hymenoptera, Vespidae) is a social wasp abundant in south and southeastern Brazilian regions, as well as in other countries such as Argentina and Paraguay. This species belongs to a large group of insects from the Hymenoptera order of medical importance. There is high risk of accidents with stings, and, depending on the amount of venom and the degree of individual’s sensitization, these accidents can lead to systemic allergic reactions, with chance of evolving to anaphylactic shock. Studies with this venom’s allergens have gained increasing interest due to the promising results of its use in laboratorial diagnosis, as well as in clinical protocols of allergen-specific immunotherapy. Among the components of P. paulista venom, the protein antigen 5 (Poly p 5) has been considered one of the main allergens present in this species. However, studies are needed to enlighten the biological and functional role of this antigen in the context of hypersensitivity reactions to the venom. Thus, in this work we evaluated the potential pro or anti-inflammatory effect of the allergen antigen 5 of P. paulista, expressed in recombinant form (rPoly p 5) in yeast Komagataella phaffi, on macrophages differentiated from precursor cells present in mouse bone marrow (BM-M), activated and not activated with pro-inflammatory stimuli. For this purpose, changes in cell viability, phagocytic capacity, production of nitric oxide (NO) and pro-inflammatory cytokines were analyzed in these cells, in addition to the expression of the co-stimulatory molecules CD80 and CD86. The results obtained indicate that rPoly p 5 does not significantly affect NO production in BM-M activated or not with pro-inflammatory stimuli. However, it caused a reduction in the frequency of cells expressing the co-stimulatory molecules CD86 and CD80 in activated and nonactivated BM-M with pro-inflammatory stimuli, respectively. In addition, rPoly p 5 induced an increase in the expression of IL-23 and IL-27 in non-activated BM-M, and of GM-CSF in activated BM-M, and reduced the expression of MCP-1 in activated BMM. These findings may indicate an important role of this allergen in the polarization of functional macrophages phenotypes under different stimuli, activated and nonactivated. In this sense, from the analysis of BM-M responses regarding rPoly p 5 pro or anti-inflammatory potential, it can be concluded that the results obtained here may help understand this protein’s immunomodulatory potential in important components of innate immunity.
Polybia paulista (Hymenoptera, Vespidae) is a social wasp abundant in south and southeastern Brazilian regions, as well as in other countries such as Argentina and Paraguay. This species belongs to a large group of insects from the Hymenoptera order of medical importance. There is high risk of accidents with stings, and, depending on the amount of venom and the degree of individual’s sensitization, these accidents can lead to systemic allergic reactions, with chance of evolving to anaphylactic shock. Studies with this venom’s allergens have gained increasing interest due to the promising results of its use in laboratorial diagnosis, as well as in clinical protocols of allergen-specific immunotherapy. Among the components of P. paulista venom, the protein antigen 5 (Poly p 5) has been considered one of the main allergens present in this species. However, studies are needed to enlighten the biological and functional role of this antigen in the context of hypersensitivity reactions to the venom. Thus, in this work we evaluated the potential pro or anti-inflammatory effect of the allergen antigen 5 of P. paulista, expressed in recombinant form (rPoly p 5) in yeast Komagataella phaffi, on macrophages differentiated from precursor cells present in mouse bone marrow (BM-M), activated and not activated with pro-inflammatory stimuli. For this purpose, changes in cell viability, phagocytic capacity, production of nitric oxide (NO) and pro-inflammatory cytokines were analyzed in these cells, in addition to the expression of the co-stimulatory molecules CD80 and CD86. The results obtained indicate that rPoly p 5 does not significantly affect NO production in BM-M activated or not with pro-inflammatory stimuli. However, it caused a reduction in the frequency of cells expressing the co-stimulatory molecules CD86 and CD80 in activated and nonactivated BM-M with pro-inflammatory stimuli, respectively. In addition, rPoly p 5 induced an increase in the expression of IL-23 and IL-27 in non-activated BM-M, and of GM-CSF in activated BM-M, and reduced the expression of MCP-1 in activated BMM. These findings may indicate an important role of this allergen in the polarization of functional macrophages phenotypes under different stimuli, activated and nonactivated. In this sense, from the analysis of BM-M responses regarding rPoly p 5 pro or anti-inflammatory potential, it can be concluded that the results obtained here may help understand this protein’s immunomodulatory potential in important components of innate immunity.
Descrição
Palavras-chave
Hymenoptera, Polybia paulista, Antígeno 5, Macrófagos, Imunomodulação, Resposta alérgica, Antigen 5, Macrophages, Immunomodulatory, Allergy