Lena Fischer-Riepe1, Niklas Daber1, Jonas Schulte-Schrepping2, Bruna Caroline Véras De Carvalho1, Antonella Russo1, Michele Pohlen3, Josephine Fischer4, Achmet Imam Chasan1, Marc Wolf1, Thomas Ulas2, Shirin Glander5, Christian Schulz6, Boris Skryabin7, Andreas Wollbrink Dipl-Ing8, Nadine Steingraeber8, Christopher Stremmel9, Megan Koehle9, Florian Gärtner9, Sabine Vettorazzi10, Dirk Holzinger1, Joachim Gross8, Frank Rosenbauer4, Monika Stoll5, Silke Niemann11, Jan Tuckermann10, Joachim L Schultze12, Johannes Roth13, Katarzyna Barczyk-Kahlert14. 1. Institute of Immunology, University of Muenster, Muenster, Germany. 2. Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany. 3. Institute of Immunology, University of Muenster, Muenster, Germany; Department of Medicine A, Hematology and Oncology, University Hospital of Muenster, Muenster, Germany. 4. Institute of Molecular Tumor Biology, University of Muenster, Muenster, Germany. 5. Institute of Human Genetics, Genetic Epidemiology, University of Muenster, Muenster, Germany. 6. Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany. 7. Department of Medicine, Transgenic Animal and Genetic Engineering Models, University of Muenster, Muenster, Germany. 8. Institute for Biomagnetism and Biosignalanalysis, University of Muenster, Muenster, Germany. 9. Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany. 10. Institute of Comparative Molecular Endocrinology (CME), University of Ulm, Ulm, Germany. 11. Institute of Medical Microbiology, University Hospital Muenster, Muenster, Germany. 12. Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany; Platform for Single Cell Genomics and Epigenomics (PRECISE) at the DZNE and the University of Bonn, Bonn, Germany. 13. Institute of Immunology, University of Muenster, Muenster, Germany; Interdisciplinary Centre for Clinical Research, University of Muenster, Muenster, Germany. 14. Institute of Immunology, University of Muenster, Muenster, Germany. Electronic address: bar@uni-muenster.de.
Abstract
BACKGROUND: Scavenger receptor CD163 is exclusively expressed on monocytes/macrophages and is widely used as a marker for alternatively activated macrophages. However, the role of CD163 is not yet clear. OBJECTIVES: We sought to examine the function of CD163 in steady-state as well as in sterile and infectious inflammation. METHODS: Expression of CD163 was analyzed under normal and inflammatory conditions in mice. Functional relevance of CD163 was investigated in models of inflammation in wild-type and CD163-/- mice. RESULTS: We describe a subpopulation of bone marrow-resident macrophages (BMRMs) characterized by a high expression of CD163 and functionally distinct from classical bone marrow-derived macrophages. Development of CD163+ BMRMs is strictly dependent on IFN regulatory factor-8. CD163+ BMRMs show a specific transcriptome and cytokine secretion pattern demonstrating a specific immunomodulatory profile of these cells. Accordingly, CD163-/- mice show a stronger inflammation in allergic contact dermatitis, indicating a regulatory role of CD163. However, CD163-/- mice are highly susceptible to S aureus infections, demonstrating the relevance of CD163 for antimicrobial defense as well. CONCLUSIONS: Our data indicate that anti-inflammatory and immunosuppressive mechanisms are not necessarily associated with a decreased antimicrobial activity. In contrast, our data define a novel macrophage population that controls overwhelming inflammation on one hand but is also necessary for an effective control of infections on the other hand.
BACKGROUND: Scavenger receptor CD163 is exclusively expressed on monocytes/macrophages and is widely used as a marker for alternatively activated macrophages. However, the role of CD163 is not yet clear. OBJECTIVES: We sought to examine the function of CD163 in steady-state as well as in sterile and infectious inflammation. METHODS: Expression of CD163 was analyzed under normal and inflammatory conditions in mice. Functional relevance of CD163 was investigated in models of inflammation in wild-type and CD163-/- mice. RESULTS: We describe a subpopulation of bone marrow-resident macrophages (BMRMs) characterized by a high expression of CD163 and functionally distinct from classical bone marrow-derived macrophages. Development of CD163+ BMRMs is strictly dependent on IFN regulatory factor-8. CD163+ BMRMs show a specific transcriptome and cytokine secretion pattern demonstrating a specific immunomodulatory profile of these cells. Accordingly, CD163-/- mice show a stronger inflammation in allergic contact dermatitis, indicating a regulatory role of CD163. However, CD163-/- mice are highly susceptible to S aureus infections, demonstrating the relevance of CD163 for antimicrobial defense as well. CONCLUSIONS: Our data indicate that anti-inflammatory and immunosuppressive mechanisms are not necessarily associated with a decreased antimicrobial activity. In contrast, our data define a novel macrophage population that controls overwhelming inflammation on one hand but is also necessary for an effective control of infections on the other hand.
Authors: Srikanth Mairpady Shambat; Alejandro Gómez-Mejia; Tiziano A Schweizer; Markus Huemer; Chun-Chi Chang; Claudio Acevedo; Judith Bergada-Pijuan; Clément Vulin; Daniel A Hofmaenner; Thomas C Scheier; Sanne Hertegonne; Elena Parietti; Nataliya Miroshnikova; Pedro D Wendel Garcia; Matthias P Hilty; Philipp Karl Buehler; Reto A Schuepbach; Silvio D Brugger; Annelies S Zinkernagel Journal: PLoS Pathog Date: 2022-01-10 Impact factor: 6.823
Authors: Kenneth Lundstrom; Altijana Hromić-Jahjefendić; Esma Bilajac; Alaa A A Aljabali; Katarina Baralić; Nagwa A Sabri; Eslam M Shehata; Mohamed Raslan; Ana Cláudia B H Ferreira; Ángel Serrano-Aroca; Murtaza M Tambuwala; Vladimir N Uversky; Vasco Azevedo; Khalid J Alzahrani; Khalaf F Alsharif; Ibrahim F Halawani; Fuad M Alzahrani; Debmalya Barh Journal: Cell Signal Date: 2022-10-14 Impact factor: 4.850