Intestinal host defense outcome is dictated by PGE 2 production during efferocytosis of infected cells.

Autor: Dejani NN; Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, 01049-010 São Paulo, Brazil.; Department of Biochemistry and Immunology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, 14049-900 São Paulo, Brazil., Orlando AB; Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, 01049-010 São Paulo, Brazil., Niño VE; Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, 01049-010 São Paulo, Brazil., Penteado LA; Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, 01049-010 São Paulo, Brazil., Verdan FF; Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, 01049-010 São Paulo, Brazil.; Department of Biochemistry and Immunology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, 14049-900 São Paulo, Brazil., Bazzano JMR; Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, 01049-010 São Paulo, Brazil., Codo AC; Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, 01049-010 São Paulo, Brazil., Salina ACG; Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, 01049-010 São Paulo, Brazil.; Department of Biochemistry and Immunology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, 14049-900 São Paulo, Brazil., Saraiva AC; Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, 01049-010 São Paulo, Brazil., Avelar MR; Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, 01049-010 São Paulo, Brazil., Spolidorio LC; Department of Physiology and Pathology, School of Dentistry, São Paulo State University, Araraquara, 01049-010 São Paulo, Brazil., Serezani CH; Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN 37232., Medeiros AI; Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, 01049-010 São Paulo, Brazil; medeirosai@fcfar.unesp.br.
Jazyk: angličtina
Zdroj: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2018 Sep 04; Vol. 115 (36), pp. E8469-E8478. Date of Electronic Publication: 2018 Aug 20.
DOI: 10.1073/pnas.1722016115
Abstrakt: Inflammatory responses are terminated by the clearance of dead cells, a process termed efferocytosis. A consequence of efferocytosis is the synthesis of the antiinflammatory mediators TGF-β, PGE 2 , and IL-10; however, the efferocytosis of infected cells favors Th17 responses by eliciting the synthesis of TGF-β, IL-6, and IL-23. Recently, we showed that the efferocytosis of apoptotic Escherichia coli -infected macrophages by dendritic cells triggers PGE 2 production in addition to pro-Th17 cytokine expression. We therefore examined the role of PGE 2 during Th17 differentiation and intestinal pathology. The efferocytosis of apoptotic E. coli -infected cells by dendritic cells promoted high levels of PGE 2 , which impaired IL-1R expression via the EP4-PKA pathway in T cells and consequently inhibited Th17 differentiation. The outcome of murine intestinal Citrobacter rodentium infection was dependent on the EP4 receptor. Infected mice treated with EP4 antagonist showed enhanced intestinal defense against C. rodentium compared with infected mice treated with vehicle control. Those results suggest that EP4 signaling during infectious colitis could be targeted as a way to enhance Th17 immunity and host defense.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE
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