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.
We examined the function of CD163 in steady-state as well as in sterile and infectious inflammation.
Expression of CD163 was analyzed under normal and inflammatory conditions in mice. Functional relevance of CD163 was investigated in models of inflammation in wildtype and CD163 mice.
We describe a subpopulation of BM resident macrophages (BMRM) which is characterized by a high expression of CD163 and is functionally distinct from classical bone marrow-derived macrophages (BMDM). Development of CD163 BMRM is strictly dependent on interferon regulatory factor-8 (IRF8). CD163 BMRM 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. On the other hand, CD163 mice are highly susceptible to S. aureus infections demonstrating the relevance of CD163 for anti-microbial defense as well.
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 which controls overwhelming inflammation on one hand but is also necessary for an effective control of infections on the other hand.

Copyright © 2020. Published by Elsevier Inc.