23
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      GM-CSF Priming Drives Bone Marrow-Derived Macrophages to a Pro-Inflammatory Pattern and Downmodulates PGE 2 in Response to TLR2 Ligands

      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

          In response to pathogen recognition by Toll-like receptors (TLRs) on their cell surface, macrophages release lipid mediators and cytokines that are widely distributed throughout the body and play essential roles in host responses. Granulocyte macrophage colony-stimulating factor (GM-CSF) is important for the immune response during infections to improve the clearance of microorganisms. In this study, we examined the release of mediators in response to TLR2 ligands by bone marrow-derived macrophages (BMDMs) primed with GM-CSF. We demonstrated that when stimulated with TLR2 ligands, non-primed BMDMs preferentially produced PGE 2 in greater amounts than LTB 4. However, GM-CSF priming shifted the release of lipid mediators by BMDMs, resulting in a significant decrease of PGE 2 production in response to the same stimuli. The decrease of PGE 2 production from primed BMDMs was accompanied by a decrease in PGE-synthase mRNA expression and an increase in TNF-α and nitric oxide (NO) production. Moreover, some GM-CSF effects were potentiated by the addition of IFN-γ. Using a variety of TLR2 ligands, we established that PGE 2 release by GM-CSF-primed BMDMs was dependent on TLR2 co-receptors (TLR1, TLR6), CD14, MyD88 and the nuclear translocation of NFκB but was not dependent on peroxisome proliferator-activated receptor-γ (PPAR-γ) activation. Indeed, GM-CSF priming enhanced TLR2, TLR4 and MyD88 mRNA expression and phospho-IκBα formation. These findings demonstrate that GM-CSF drives BMDMs to present a profile relevant to the host during infections.

          Related collections

          Most cited references 75

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

          Toll-like receptors: critical proteins linking innate and acquired immunity.

          Recognition of pathogens is mediated by a set of germline-encoded receptors that are referred to as pattern-recognition receptors (PRRs). These receptors recognize conserved molecular patterns (pathogen-associated molecular patterns), which are shared by large groups of microorganisms. Toll-like receptors (TLRs) function as the PRRs in mammals and play an essential role in the recognition of microbial components. The TLRs may also recognize endogenous ligands induced during the inflammatory response. Similar cytoplasmic domains allow TLRs to use the same signaling molecules used by the interleukin 1 receptors (IL-1Rs): these include MyD88, IL-1R--associated protein kinase and tumor necrosis factor receptor--activated factor 6. However, evidence is accumulating that the signaling pathways associated with each TLR are not identical and may, therefore, result in different biological responses.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids.

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

              Recognition of microorganisms and activation of the immune response.

              The mammalian immune system has innate and adaptive components, which cooperate to protect the host against microbial infections. The innate immune system consists of functionally distinct 'modules' that evolved to provide different forms of protection against pathogens. It senses pathogens through pattern-recognition receptors, which trigger the activation of antimicrobial defences and stimulate the adaptive immune response. The adaptive immune system, in turn, activates innate effector mechanisms in an antigen-specific manner. The connections between the various immune components are not fully understood, but recent progress brings us closer to an integrated view of the immune system and its function in host defence.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                13 July 2012
                : 7
                : 7
                Affiliations
                [1 ]Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto – Universidade de São Paulo – Ribeirão Preto, SP – Brazil
                [2 ]CNRS, UMR6218, Orleans, France
                [3 ]Orleans University, Molecular Immunology and Embryology, Orleans, France
                University of São Paulo, Brazil
                Author notes

                Conceived and designed the experiments: CAS LHF BR VQ. Performed the experiments: CAS SR NC DC FWGPS PAA. Analyzed the data: CAS FGF FWGPS PAA. Contributed reagents/materials/analysis tools: BR VQ LHF. Wrote the paper: CAS FGF LHF BR VQ.

                Article
                PONE-D-11-13804
                10.1371/journal.pone.0040523
                3396658
                22808181
                Sorgi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                Page count
                Pages: 13
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Immune Physiology
                Cytokines
                Developmental Biology
                Molecular Development
                Cytokines
                Immunology
                Immune Cells
                Monocytes
                Immune System
                Bone Marrow
                Cytokines
                Immunity
                Immune Defense
                Immunity to Infections
                Inflammation
                Innate Immunity
                Immune Response
                Immunomodulation
                Microbiology
                Immunity
                Inflammation
                Innate Immunity
                Medicine
                Anatomy and Physiology
                Immune Physiology
                Cytokines
                Clinical Immunology
                Immune System
                Cytokines
                Immunity
                Inflammation
                Innate Immunity

                Uncategorized

                Comments

                Comment on this article