9
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Transcriptional Responses in the Murine Spleen after Toxoplasma gondii Infection: Inflammasome and Mucus-Associated Genes

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The spleen plays an important role in coordinating both adaptive and innate immune responses. Here, the transcriptional response to T. gondii infection in the murine spleen was characterized concerning inflammasome sensors (two different models: seven days after oral or four weeks after intraperitoneal infection). Additionally, Tff1 KO and Tff3 KO mice were investigated because TFF genes are often upregulated during inflammation. The expression of the pattern-recognition receptors Nlrp3, Nlrp12, and Nlrp1a was significantly increased after infection. This increase was diminished in Tff1 KO and Tff3 KO mice pointing towards a positive regulation of the inflammatory response by Tff1 and Tff3. Furthermore, the transcription of Tff1 (encoding a motogenic lectin) and other secretory genes was analyzed, i.e., gastrokines ( Gkn), IgG Fc binding protein ( Fcgbp), and the mucin Muc2. The corresponding gene products belong to an interactome protecting mucous epithelia. Tff1 was significantly induced after infection, which might increase the motility of immune cells. In contrast, Gkn3, Fcgbp, and Muc2 were downregulated seven days after oral infection; whereas four weeks after i.p. infection only Gkn3 remained downregulated. This might be an indication that Gkn3, Fcgbp, and Muc2 are involved in the transient disruption of the splenic architecture and its reorganization, which is characteristic after T. gondii infection.

          Related collections

          Most cited references55

          • Record: found
          • Abstract: found
          • Article: not found

          The spleen in local and systemic regulation of immunity.

          The spleen is the main filter for blood-borne pathogens and antigens, as well as a key organ for iron metabolism and erythrocyte homeostasis. Also, immune and hematopoietic functions have been recently unveiled for the mouse spleen, suggesting additional roles for this secondary lymphoid organ. Here we discuss the integration of the spleen in the regulation of immune responses locally and in the whole body and present the relevance of findings for our understanding of inflammatory and degenerative diseases and their treatments. We consider whether equivalent activities in humans are known, as well as initial therapeutic attempts to target the spleen for modulating innate and adaptive immunity. Copyright © 2013 Elsevier Inc. All rights reserved.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis

            The innate immune system protects against infection and tissue injury through the specialized organs of the reticuloendothelial system, including the lungs, liver, and spleen. The central nervous system regulates innate immune responses via the vagus nerve, a mechanism termed the cholinergic antiinflammatory pathway. Vagus nerve stimulation inhibits proinflammatory cytokine production by signaling through the α7 nicotinic acetylcholine receptor subunit. Previously, the functional relationship between the cholinergic antiinflammatory pathway and the reticuloendothelial system was unknown. Here we show that vagus nerve stimulation fails to inhibit tumor necrosis factor (TNF) production in splenectomized animals during lethal endotoxemia. Selective lesioning of the common celiac nerve abolishes TNF suppression by vagus nerve stimulation, suggesting that the cholinergic pathway is functionally hard wired to the spleen via this branch of the vagus nerve. Administration of nicotine, an α7 agonist that mimics vagus nerve stimulation, increases proinflammatory cytokine production and lethality from polymicrobial sepsis in splenectomized mice, indicating that the spleen is critical to the protective response of the cholinergic pathway. These results reveal a specific, physiological connection between the nervous and innate immune systems that may be exploited through either electrical vagus nerve stimulation or administration of α7 agonists to inhibit proinflammatory cytokine production during infection and tissue injury.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Proteomic analyses of the two mucus layers of the colon barrier reveal that their main component, the Muc2 mucin, is strongly bound to the Fcgbp protein.

              The colon epithelium is protected from the luminal microbes as recently revealed by an inner firmly attached mucus layer impervious to bacteria and an outer loose mucus layer that is the habitat of bacteria. For an additional understanding of these layers, we analyzed the protein composition of these two mucus layers from the mouse colon. Proteomics using nano-LC-MS and MS/MS revealed more than 1000 protein entries. As the mucus layers contain detached cells, a majority of the proteins had an intracellular origin. However, at least 44 entries were described as secreted proteins and predicted to be mucus constituents together with extracellular/plasma and bacterial proteins, the latter largely in the loose mucus layer. A major protein was the Muc2 mucin that by its net-like disulfide-bonded polymer structure builds the mucus. When guanidinium chloride insoluble Muc2 units were analyzed, N-terminal parts of the Fc-gamma binding protein (Fcgbp) was found to be covalently attached in mouse and human colon, whereas its C-terminus was lost by reducing the disulfide bonds. In conclusion, the Fcgbp protein is probably cleaved at GD/PH and covalently attached to Muc2 via one or several of its von Willebrand D domains.
                Bookmark

                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                10 June 2017
                June 2017
                : 18
                : 6
                : 1245
                Affiliations
                [1 ]Institute of Molecular Biology and Medicinal Chemistry, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany; eva.znalesniak@ 123456med.ovgu.de (E.B.Z.); ftketty@ 123456gmail.com (T.F.); franz.salm@ 123456med.ovgu.de (F.S.)
                [2 ]Institute of Medical Microbiology and Hygiene, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany; ulrike.haendel@ 123456med.ovgu.de
                Author notes
                [†]

                These authors contributed equally to this work.

                Article
                ijms-18-01245
                10.3390/ijms18061245
                5486068
                28604600
                3bcd7f0f-af29-4234-a055-7f9075632171
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 26 April 2017
                : 03 June 2017
                Categories
                Communication

                Molecular biology
                inflammation,inflammasome,tff1,trefoil factor,toxoplasma gondii,gastrokine,igg fc binding protein,muc2

                Comments

                Comment on this article