CD163 expression defines specific, IRF8-dependent, immune-modulatory macrophages in the bone marrow

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.

Keywords: IFN regulatory factor 8; Resident bone marrow macrophages; scavenger receptor CD163; sterile and systemic inflammation.