Figure 1.

The different functions of CD169⁺ macrophages and their cross-talk with cDC1. (1) Uptake: CD169⁺ macrophages capture and phagocytose pathogens, including bacteria and viruses, as well as dead cells. The CD169 molecule also directly binds to exosomes and specific pathogens, such as HIV. (2) Antigen transfer: CD169⁺ macrophages directly interact and present antigens to cDC1s for the generation of antigen-specific CD8⁺ T cell responses. While HIV particles are transferred via CD169, other components of bacteria and viruses can be transferred to cDC1s from the macrophages. Dead cells can stimulate cDC1s via CLEC9A expressed on the cDC1. The interaction between CD169⁺ macrophages and cDC1s is dependent on binding of CD169 to sialic acid structures on cDC1s. (3) IFN-I priming: after encounter with bacteria, dead cells, or viruses, CD169⁺ macrophages secrete IFN-I that is required for optimal activation of cDC1s and T cells. Subsequently, pDCs are recruited and their IFN-I production further amplifies the signal. (4) Trans-infection: in the case of HIV and MLV, CD169⁺ macrophages can also mediate viral trans-infection to CD4 T cells and B cells.