Abstract
Most tissues harbor resident mononuclear phagocytes, that is, dendritic cells and macrophages. A classification that sufficiently covers their phenotypic heterogeneity and plasticity during homeostasis and disease does not yet exist because cell culture-based phenotypes often do not match those found in vivo. The plasticity of mononuclear phagocytes becomes obvious during dynamic or complex disease processes. Different data interpretation also originates from different conceptual perspectives. An immune-centric view assumes that a particular priming of phagocytes then causes a particular type of pathology in target tissues, conceptually similar to antigen-specific T-cell priming. A tissue-centric view assumes that changing tissue microenvironments shape the phenotypes of their resident and infiltrating mononuclear phagocytes to fulfill the tissue's need to maintain or regain homeostasis. Here we discuss the latter concept, for example, why different organs host different types of mononuclear phagocytes during homeostasis. We further discuss how injuries alter tissue environments and how this primes mononuclear phagocytes to enforce this particular environment, for example, to support host defense and pathogen clearance, to support the resolution of inflammation, to support epithelial and mesenchymal healing, and to support the resolution of fibrosis to the smallest possible scar. Thus, organ- and disease phase-specific microenvironments determine macrophage and dendritic cell heterogeneity in a temporal and spatial manner, which assures their support to maintain and regain homeostasis in whatever condition. Mononuclear phagocytes contributions to tissue pathologies relate to their central roles in orchestrating all stages of host defense and wound healing, which often become maladaptive processes, especially in sterile and/or diffuse tissue injuries.
Highlights
Mononuclear phagocytes are a group of phenotypic distinct members, often referred to as either macrophages or dendritic cells (DC), that derive from myeloid precursors and that contribute to the functions of peripheral tissues [1]
We examine tissue needs to maintain homeostasis and how to regain homeostasis upon tissue injury
When tissue injuries alter the organspecific tissue environment, the resident as well as the infiltrating myeloid cells will be affected as a result of their plasticity to polarize to different phenotypes in different environments
Summary
Mononuclear phagocytes are a group of phenotypic distinct members, often referred to as either macrophages or dendritic cells (DC), that derive from myeloid precursors and that contribute to the functions of peripheral tissues [1]. We discuss how published data supports the view that changing tissue environments induce the wellknown different phenotypes of mononuclear phagocytes, a process that enforces each of the different environments and explains the contribution of these cells to the different tissue pathologies. This slightly different perspective may somewhat shape our understanding of macrophage heterogeneity and tissue pathology but certainly raise new questions for future research
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