CD169+ Macrophages Capture and Dendritic Cells Instruct: The Interplay of the Gatekeeper and the General of the Immune System

Abstract

Since the seminal discovery of dendritic cells (DCs) by Steinman and Cohn in 1973, there has been an ongoing debate to what extent macrophages and DCs are related and perform different functions. The current view is that macrophages and DCs originate from different lineages and that only DCs have the capacity to initiate adaptive immunity. Nevertheless, as we will discuss in this review, lymphoid tissue resident CD169+ macrophages have been shown to act in concert with DCs to promote or suppress adaptive immune responses for pathogens and self-antigens, respectively. Accordingly, we propose a functional alliance between CD169+ macrophages and DCs in which a division of tasks is established. CD169+ macrophages are responsible for the capture of pathogens and are frequently the first cell type infected and thereby provide a confined source of antigen. Subsequently, cross-presenting DCs interact with these antigen-containing CD169+ macrophages, pick up antigens and activate T cells. The cross-priming of T cells by DCs is enhanced by the localized production of type I interferons (IFN-I) derived from CD169+ macrophages and plasmacytoid DCs (pDCs) that induces DC maturation. The interaction between CD169+ macrophages and DCs appears not only to be essential for immune responses against pathogens, but also plays a role in the induction of self-tolerance and immune responses against cancer. In this review we will discuss the studies that demonstrate the collaboration between CD169+ macrophages and DCs in adaptive immunity.

Commensal microbiota drive the functional diversification of colon macrophages

“…26 In contrast, in non-intestinal lymphoid tissues, expression of CD169 by MPs can be driven by type-1 IFNs during viral infections but is constitutively expressed by marginal-zone and subcapsularsinus MPs that require B cell-produced LTα1β2, as well as RANK, LXR, and CSF-1 signaling. 39 Other specific signals that may be important for MP differentiation is implied by our analysis of regulons important for these divergent differentiation pathways, and upstream analysis of these pathways is complex, and currently being evaluated.…”

“…We next determined the ability of these two colon MP subpopulations to capture systemic antigens, since prior studies had identified CD169 + MPs in the spleen and LNs as "gatekeepers" at the blood-LN interface. 38,39 F4/80 + cells closely associated with blood vessels avidly took up systemically administered 10kD dextran (Dex) ( Fig. 3c), which was further localized to the CD11c − CD169 + CD206 hi cell population ( Fig.…”

Why isListeria monocytogenessuch a potent inducer of CD8+ T‐cells?

“…In coordination with DCs, CD169+ macrophages support CMI by providing antigen and producing type I IFN. However, CD169+ macrophages can suppress CMI to self‐antigens and phagosome‐restricted content including apoptotic cells and exosomes (Grabowska, Lopez‐Venegas, Affandi, & den Haan, ; McGaha, Chen, Ravishankar, van Rooijen, & Karlsson, ; Miyake et al, ; Saunderson, Dunn, Crocker, & McLellan, ). Indeed, several hours after infection, phagosome confined LLO‐minus bacteria are still localised to CD169+ macrophages, whereas bacteria growing in the host cytosol are transferred to CD8‐α + DCs that serve as a protective niche for bacterial survival (Edelson et al, ; Neuenhahn et al, ; Perez et al, ).…”

Regulation of Macrophage and Dendritic Cell Function by Chondroitin Sulfate in Innate to Antigen-Specific Adaptive Immunity

“…In general, macrophages remain at the inflammatory sites to eliminate pathogens and apoptotic cells by phagocytosis and clearance and produce pro-inflammatory cytokines. In contrast, DCs can travel to the draining lymph nodes and stimulate T cells (28,29).…”