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Bacterial and Metabolic Factors of Staphylococcal Planktonic and Biofilm Environments Differentially Regulate Macrophage Immune Activation.
Seebach, Elisabeth; Elschner, Tabea; Kraus, Franziska V; Souto-Carneiro, Margarida; Kubatzky, Katharina F.
Afiliação
  • Seebach E; Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University, Im Neuenheimer Feld 324, 69120, Heidelberg, Germany. elisabeth.seebach@med.uni-heidelberg.de.
  • Elschner T; Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University, Im Neuenheimer Feld 324, 69120, Heidelberg, Germany.
  • Kraus FV; Current address: Institute for Cardiovascular Sciences & Institute of Neurovascular Cell Biology (INVZ), University Hospital Bonn, University of Bonn, Bonn, Germany.
  • Souto-Carneiro M; Department of Internal Medicine 5 - Hematology Oncology Rheumatology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
  • Kubatzky KF; Department of Internal Medicine 5 - Hematology Oncology Rheumatology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
Inflammation ; 46(4): 1512-1530, 2023 Aug.
Article em En | MEDLINE | ID: mdl-37212952
Biofilm formation is a leading cause for chronic implant-related bone infections as biofilms shield bacteria against the immune system and antibiotics. Additionally, biofilms generate a metabolic microenvironment that shifts the immune response towards tolerance. Here, we compared the impact of the metabolite profile of bacterial environments on macrophage immune activation using Staphylococcus aureus (SA) and epidermidis (SE) conditioned media (CM) of planktonic and biofilm cultures. The biofilm environment had reduced glucose and increased lactate concentrations. Moreover, the expression of typical immune activation markers on macrophages was reduced in the biofilm environment compared to the respective planktonic CM. However, all CM caused a predominantly pro-inflammatory macrophage cytokine response with a comparable induction of Tnfa expression. In biofilm CM, this was accompanied by higher levels of anti-inflammatory Il10. Planktonic CM, on the other hand, induced an IRF7 mediated Ifnb gene expression which was absent in the biofilm environments. For SA but not for SE planktonic CM, this was accompanied by IRF3 activation. Stimulation of macrophages with TLR-2/-9 ligands under varying metabolic conditions revealed that, like in the biofilm setting, low glucose concentration reduced the Tnfa to Il10 mRNA ratio. However, the addition of extracellular L-lactate but not D-lactate increased the Tnfa to Il10 mRNA ratio upon TLR-2/-9 stimulation. In summary, our data indicate that the mechanisms behind the activation of macrophages differ between planktonic and biofilm environments. These differences are independent of the metabolite profiles, suggesting that the production of different bacterial factors is ultimately more important than the concentrations of glucose and lactate in the environment.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções Estafilocócicas / Interleucina-10 Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções Estafilocócicas / Interleucina-10 Idioma: En Ano de publicação: 2023 Tipo de documento: Article