1. CD163 expression defines specific, IRF8-dependent, immune-modulatory macrophages in the bone marrow
- Author
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Nadine Steingraeber, Antonella Russo, Dirk Holzinger, Lena Fischer-Riepe, Achmet Imam Chasan, Frank Rosenbauer, Thomas Ulas, Megan Koehle, Monika Stoll, Jonas Schulte-Schrepping, Shirin Glander, Joachim Gross, Boris V. Skryabin, Christopher Stremmel, Johannes Roth, Dipl-Ing Andreas Wollbrink, Sabine Vettorazzi, Silke Niemann, Florian Gärtner, Michele Pohlen, Niklas Daber, Bruna Caroline Véras De Carvalho, Christian Schulz, Marc Wolf, Joachim L. Schultze, Jan Tuckermann, Josephine Fischer, and Katarzyna Barczyk-Kahlert
- Subjects
0301 basic medicine ,immunology [Dermatitis, Allergic Contact] ,metabolism [Antigens, CD] ,metabolism [Receptors, Cell Surface] ,immunology [Bone Marrow Cells] ,Bone marrow-derived macrophage ,Mice ,immunology [Inflammation] ,genetics [Interferon Regulatory Factors] ,immunology [Staphylococcal Infections] ,Immunology and Allergy ,CD163 antigen ,scavenger receptor CD163 ,physiology [Staphylococcus aureus] ,Cells, Cultured ,Mice, Knockout ,Mice, Inbred BALB C ,Resident bone marrow macrophages ,Staphylococcal Infections ,immunology [Macrophages] ,medicine.anatomical_structure ,metabolism [Bone Marrow Cells] ,Dermatitis, Allergic Contact ,genetics [Receptors, Cell Surface] ,Interferon Regulatory Factors ,Cytokines ,Disease Susceptibility ,medicine.symptom ,genetics [Antigens, Differentiation, Myelomonocytic] ,Macrophage colony-stimulating factor ,IFN regulatory factor 8 ,Staphylococcus aureus ,Immunology ,Antigens, Differentiation, Myelomonocytic ,Bone Marrow Cells ,Inflammation ,Receptors, Cell Surface ,Biology ,Immunomodulation ,03 medical and health sciences ,Immune system ,Antigens, CD ,medicine ,Animals ,Humans ,ddc:610 ,Scavenger receptor ,030102 biochemistry & molecular biology ,metabolism [Interferon Regulatory Factors] ,Macrophages ,sterile and systemic inflammation ,metabolism [Cytokines] ,Macrophage Activation ,metabolism [Antigens, Differentiation, Myelomonocytic] ,interferon regulatory factor-8 ,genetics [Antigens, CD] ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,metabolism [Macrophages] ,Cytokine secretion ,Bone marrow ,Transcriptome ,CD163 - 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.
- Published
- 2020