The Scavenger Receptor MARCO Modulates TLR-Induced Responses in Dendritic Cells

Abstract

The scavenger receptor MARCO mediates macrophage recognition and clearance of pathogens and their polyanionic ligands. However, recent studies demonstrate MARCO expression and function in dendritic cells, suggesting MARCO might serve to bridge innate and adaptive immunity. To gain additional insight into the role of MARCO in dendritic cell activation and function, we profiled transcriptomes of mouse splenic dendritic cells obtained from MARCO deficient mice and their wild type counterparts under resting and activating conditions. In silico analysis uncovered major alterations in gene expression in MARCO deficient dendritic cells resulting in dramatic alterations in key dendritic cell-specific pathways and functions. Specifically, changes in CD209, FCGR4 and Complement factors can have major consequences on DC-mediated innate responses. Notably, these perturbations were magnified following activation with the TLR-4 agonist lipopolysaccharide. To validate our in silico data, we challenged DC‘s with various agonists that recognize all mouse TLRs and assessed expression of a set of immune and inflammatory marker genes. This approach identified a differential contribution of MARCO to TLR activation and validated a major role for MARCO in mounting an inflammatory response. Together, our data demonstrate that MARCO differentially affects TLR-induced DC activation and suggest targeting of MARCO could lead to different outcomes that depend on the inflammatory context encountered by DC.

Telomere profiles and tumor-associated macrophages with different immune signatures affect prognosis in glioblastoma

“…52 However, MARCO does not exclusively exist on M2 macrophages being associated with M1 and dendritic cell activation. [53][54][55] Increased CXCL12 promotes neo-angiogenesis, and supported by increased expression of SRPX2, may also mediate angiogenesis providing further evidence that tumorassociated macrophages in telomerase with macrophages are more tumor-promoting compared with those in alternative lengthening of telomeres with macrophages. 56,57 Telomerase with macrophage tumors were associated with a reduced extent of surgical resection, suggesting tumor-associated macrophages in telomerase with macrophages are more infiltrative and thus damaging.…”

Dendritic Cells in Anticancer Vaccination: Rationale for Ex Vivo Loading or In Vivo Targeting

“…Many SR ligands are also recognized by and trigger cell signaling through TLRs. It has been demonstrated that SRs internalize such ligands to render them accessible to TLR3, TLR7/8 and TLR9 localized in the cytosol [146,147]. Taking into account such findings, SRs were also proposed as a potential target for anticancer vaccine delivery to DCs.…”

Association of decreased expression of the macrophage scavenger receptor MARCO with tumor progression and poor prognosis in human hepatocellular carcinoma

“…MARCO is expressed on restricted subsets of macrophages, and its expression can be induced at sites of inflammation after bacterial infection . Moreover, MARCO seems to play a role in inflammatory responses other than the typical functions of macrophage recognition and clearance of pathogens and their polyanionic ligands . Mice deficient in MARCO exhibit significantly impaired clearance of Streptococcus pneumonia from the nasopharynx and abrogated cytokine production and cellular recruitment to the nasopharynx following colonization .…”

“…3 Moreover, MARCO seems to play a role in inflammatory responses other than the typical functions of macrophage recognition and clearance of pathogens and their polyanionic ligands. 4 Mice deficient in MARCO exhibit significantly impaired clearance of Streptococcus pneumonia from the nasopharynx and abrogated cytokine production and cellular recruitment to the nasopharynx following colonization. 5 MARCO and SR-AI/II are required for silica-induced mast cell activation, leading to the production of tumor necrosis factor-α and reactive oxygen species.…”