O papel dos receptores FcγRIIB e FcγRIII na lesão induzida por isquemia e reperfusão intestinal

• Ano de defesa: 2017
• Autor(a) principal: Camila Bernardo de Brito
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; ICB - DEPARTAMENTO DE MICROBIOLOGIA; Programa de Pós-Graduação em Microbiologia; UFMG
• Palavras-chave em Português: microbiota intestinal; inflamação; isquemia e reperfusão; Microbiologia; Isquemia; Reperfusão; Microbioma Gastrointestinal; Inflamação
• Link de acesso: http://hdl.handle.net/1843/33767

Intestinal ischemia and reperfusion (IRI) is accompanied by an exacerbated inflammatory response characterized by the influx of neutrophils and release of inflammatory mediators into the intestinal tissue resulting in tissue injury and death. The indigenous microbiota is an essential part for the control of this inflammatory response, since Germ-free mice (GF) present attenuation of local or systemic lesion after IRI. Part of inflammatory hyporresponsiveness of GF versus IRI animals is associated with a lower concentration of auto-reactive natural antibodies induced by microbiota, which are also essential for triggering reperfusion injury, since these antibodies are able to recognize neoantigens that are exposed by ischemia and deposited into intestinal tissue. However, it is not yet known whether these deposited antibodies are capable of activating FcR receptors. Therefore, the objective of our study was to evaluate the role of FcRIII and FcRIIB receptors in intestinal reperfusion injury. Our results showed that the IRI injury led to deposition of IgG in intestinal tissue, suggesting that the Fc receptors could play an important role in this inflammatory pathology. Thus, we observed that FcᵧRIII- /- mice were protected from intestinal reperfusion injury, presenting higher survival rates and less tissue injury, as well as lower influx of neutrophils and release of proinflammatory mediators into the intestinal tissue. On the other hand, we observed that FcᵧRIIB-/- presented earlier and higher lethality rates than WT mice during intestinal reperfusion injury. This higher lethality was associated with a greater tissue injury and bacterial translocation to other organs. The increased susceptibility to reperfusion injury in FcᵧRIIB -/- mice was associated with increased IgG deposition in intestinal tissue and changes in the amount and repertoire of circulating IgG in these animals, suggesting that FcᵧRIIB controls the generation of injury-promoting IgG. Interestingly, we have also observed that the intestinal microbiota is involved in controlling the production of autoantibodies in FcγRIIB animals. Thus, we can conclude that Fcᵧ receptors play an important role in IRI-induced injury.