Human macrophage galactose-type lectin (MGL) regulates macrophage inflammatory responses by balancing M1 and M2 polarization 4804

Abstract Description The macrophage galactose-type lectin (MGL) receptor is a C-type lectin receptor (CLR) expressed on macrophages and dendritic cells that is associated with regulatory function. The role of human MGL has been described in the field of cancer biology, but studies of the contribution to infectious disease processes are limited. A murine homologue, MGL-1, has been used as a model for the MGL receptor during infection with Mycobacterium tuberculosis (Mtb) and other pathogens. Findings to date suggest that MGL-1 may limit pathology and inflammation, consistent with a regulatory role. Macrophages play a pivotal role in regulating initiation and resolution of inflammation, and their function is tightly linked to M1 or M2 phenotype. Whether MGL functions are conserved in human cells, however, has yet to be reported. We observe that monocyte-derived macrophages from peripheral blood of healthy donors increase MGL following exposure to both M1 (IFN-g and LPS) or M2 (IL-4) polarizing conditions. Flow cytometric analysis further demonstrates co-expression of MGL with known M1 and M2 markers that varies with activation conditions, including the mannose receptor (MR), CD163+ cells, and CD80+ cells. In preliminary experiments, MGL-deficient THP cells demonstrated a bias toward M1 phenotype. These results suggest that MGL may regulate inflammatory responses to infection through effects on macrophage polarization. Funding Sources NIH/NIAID R33AI138328, R61AI138328 McLaughlin Fellowship: Inst. for Human Infections and Immunity, UTMB Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)