Papel das células iNKT sobre o efeito imunomodulador da Propionibacterium acnes na resposta alérgica experimental

• Ano de defesa: 2017
• Autor(a) principal: Gomes, Gabriela Martins Costa [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Corynebacterium parvum; Hypersensitivity; Immunomodulation; Natural killer T-cells; Células iNKT; Hipersensibilidade; Imunomodulação; Células T matadoras naturais
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=5081553; http://repositorio.unifesp.br/handle/11600/50710

The use of adjuvants to modulate the immune response has been used for decades, among which we can mention Propionibacterium acnes previously classified as Corynebacterium parvum, a Gram-positive anaerobic bacillus belonging to the human cutaneous microbiota. The bacterium suspension heatkilled or phenol-killed has the ability to modulate various functions of the innate and adaptive immune response demonstrated in clinical and experimental studies. In these studies the bacterium's ability to modulate the immune response induced a Th1 profile. However, in our laboratory in a murine model ovalbumin-induced type I hypersensitivity it was demonstrated that the bacterium was able to exacerbate the reaction to OVA (Th2 profile) when simultaneously administered with the sensitization of the animals, or suppress it inducing a Th1 profile when administered a week prior the sensitization with OVA. Thus, the modulation made by the bacteria in the different treatments induced differences in the moment of antigen presentation, acting directly or indirectly on professional antigen presenting cells. In addition to APCs, it can also be demonstrated in our laboratory that the bacterium modulates NKT cell functions in a murine melanoma model. Based on these studies and increasing evidence, especially in experimental asthma models, showing that iNKT cells promote and are necessary for the development of hyper reactivity and inflammation of the airways, the present study aimed to evaluate the role of iNKT cells on the allergic response to ovalbumin modulated by heat-killed P. acnes suspension. We evaluated the reaction of exacerbation or suppression induced by P. acnes in response to OVA in murine model modified by nodes. We used wild-type C57BL/6 mice, deficient in the population of NKT cells, J!18/-, CD1d-/-, and mice deficient in the migration of these CXCR6-/-. They received two subcutaneous injections, one per week, of heat-killed suspension of P. acnes simultaneously with OVA to exacerbate the allergic response. In contrast, in order to evaluate the suppression of this same reaction, these animals received two doses of heat-killed suspension of P. acnes subcutaneously with a 7-day interval between them, and one week after the last dose, they received two injections subcutaneously Of OVA being one per week. In all protocols, 7 days after the last dose the animals were challenged with OVA intraperitoneally. After 24 hours, we analyzed, in addition to the iNKT cell population, the populations of mast cells, basophils and eosinophils present in the peritoneal exudate, spleen and lymph node of the animals. It was possible to verify that in the C57B1 / 6 mice, in the exacerbation protocol, the population of iNKT cells that increased significantly was iNKT NK1.1- accompanied by a significant increase in absolute numbers of mast cells, basophils and eosinophils in the evaluated organs. In contrast, in the suppression protocol the population of iNKT cells that increased was iNKT NK1.1+ while all other populations analyzed were significantly reduced. In addition to these differences in the iNKT population in each protocol, we demonstrated that in the absence of these cells the effect of exacerbation of the P. acnes induced Th2 reaction was strongly reduced in J!18-/- and CD1d-/- animals.!However, the reconstitution of these animals submitted to the same protocols, with thymocytes from wild-type animals, the OVA exacerbation reaction induced by the bacterium was partially recovered. In this way we demonstrate that in this model the iNKT cells play a major role in the modulation exerted by P. acnes in the exacerbation of the hypersensitivity type I reaction to OVA and especially the subtype that does not express the molecule NK1.1.