Soluble CD163 masks fibronectin-binding protein A-mediated inflammatory activation of Staphylococcus aureus infected monocytes

Authors

  • Jessica Kneidl,

    1. Institute of Immunology, University of Muenster, Muenster, Germany
    2. Interdisciplinary Centre for Clinical Research, University of Muenster, Muenster, Germany
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  • Vijayashree Mysore,

    1. Institute of Immunology, University of Muenster, Muenster, Germany
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  • Jennifer Geraci,

    1. Institute of Medical Microbiology, University of Muenster, Muenster, Germany
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  • Lorena Tuchscherr,

    1. Institute of Medical Microbiology, University of Muenster, Muenster, Germany
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  • Bettina Löffler,

    1. Interdisciplinary Centre for Clinical Research, University of Muenster, Muenster, Germany
    2. Institute of Medical Microbiology, University of Muenster, Muenster, Germany
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  • Dirk Holzinger,

    1. Institute of Immunology, University of Muenster, Muenster, Germany
    2. Interdisciplinary Centre for Clinical Research, University of Muenster, Muenster, Germany
    3. Department of Pediatric Rheumatology and Immunology, University Children's Hospital, University of Muenster, Muenster, Germany
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  • Johannes Roth,

    1. Institute of Immunology, University of Muenster, Muenster, Germany
    2. Interdisciplinary Centre for Clinical Research, University of Muenster, Muenster, Germany
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  • Katarzyna Barczyk-Kahlert

    Corresponding author
    1. Institute of Immunology, University of Muenster, Muenster, Germany
    • For correspondence. E-mail bar@uni-muenster.de; Tel. (+49) (0)251 8352945; Fax (+49) (0)251 8356549.

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Summary

Binding to fibronectin (FN) is a crucial pathogenic factor of Staphylococcus aureus mediated by fibronectin-binding protein A (FnBP-A) and extracellular adherence protein (Eap). Recently, we have shown that binding of soluble CD163 (sCD163) to FN linked to these molecules exhibits anti-microbial effects by enhancing phagocytosis and killing activity of S. aureus-infected monocytes. However, it remained unclear whether sCD163 also influences the monocytic activation status. Using genetically modified staphylococcal strains we now identified FnBP-A, but not Eap, as activator of the inflammatory response of monocytes to infection. FnBP-A-mediated inflammatory activation was masked by sCD163 binding to S. aureus promoting efficient pathogen elimination. Thus, sCD163 protects monocytes from overwhelming activation upon staphylococcal infection by dampening the secretion of pro-inflammatory cytokines TNFα, IL-1β, IL-6 and IL-8 and DAMP molecule MRP8/14. Moreover, sCD163 limited expression of pro-apoptotic transcription factor NR4A1 induced during S. aureus infection and inhibited induction of chemokine CXCL2promoting survival of staphylococci in vivo. sCD163-mediated effects were not due to general immunosuppression since MAP kinase activation and ROS production were unaltered during infection of monocytes with sCD163-bound bacteria. Thus, sCD163 promotes a specific defence of the immune system against FnBP-A-mediated inflammatory activation enabling successful pathogen elimination, tissue recovery and resolution of inflammation.

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