Fc γ RIIb protects from reperfusion injury by controlling antibody and type I IFN-mediated tissue injury and death.

Autor: de Brito CB; Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Ascenção FR; Centro de Pesquisa e Desenvolvimento de Fármacos, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Arifa RDN; Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Lima RL; Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Garcia ZM; Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Fagundes M; Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.; Centro de Pesquisa e Desenvolvimento de Fármacos, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Resende BG; Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Bezerra RO; Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Queiroz-Junior CM; Centro de Pesquisa e Desenvolvimento de Fármacos, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Santos ACPMD; Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Oliveira MAP; Department of Microbiology, Immunology, Parasitology and Pathology, Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiania, Brazil., Teixeira MM; Centro de Pesquisa e Desenvolvimento de Fármacos, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Fagundes CT; Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.; Centro de Pesquisa e Desenvolvimento de Fármacos, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Souza DG; Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Jazyk: angličtina
Zdroj: Immunology [Immunology] 2022 Nov; Vol. 167 (3), pp. 428-442. Date of Electronic Publication: 2022 Jul 29.
DOI: 10.1111/imm.13547
Abstrakt: Intestinal ischemia and reperfusion (I/R) is accompanied by an exacerbated inflammatory response characterized by deposition of IgG, release of inflammatory mediators, and intense neutrophil influx in the small intestine, resulting in severe tissue injury and death. We hypothesized that Fc γ RIIb activation by deposited IgG could inhibit tissue damage during I/R. Our results showed that I/R induction led to the deposition of IgG in intestinal tissue during the reperfusion phase. Death upon I/R occurred earlier and was more frequent in Fc γ RIIb -/- than WT mice. The higher lethality rate was associated with greater tissue injury and bacterial translocation to other organs. Fc γ RIIb -/- mice presented changes in the amount and repertoire of circulating IgG, leading to increased IgG deposition in intestinal tissue upon reperfusion in these mice. Depletion of intestinal microbiota prevented antibody deposition and tissue damage in Fc γ RIIb -/- mice submitted to I/R. We also observed increased production of ROS on neutrophils harvested from the intestines of Fc γ RIIb -/- mice submitted to I/R. In contrast, Fc γ RIII -/- mice presented reduced tissue damage and neutrophil influx after reperfusion injury, a phenotype reversed by Fc γ RIIb blockade. In addition, we observed reduced IFN-β expression in the intestines of Fc γ RIII -/- mice after I/R, a phenotype that was also reverted by blocking Fc γ RIIb. IFNAR -/- mice submitted to I/R presented reduced lethality and TNF release. Altogether our results demonstrate that antibody deposition triggers Fc γ RIIb to control IFN-β and IFNAR activation and subsequent TNF release, tailoring tissue damage, and death induced by reperfusion injury.
(© 2022 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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