Novel Anti-bacterial and Anti-inflammatory Roles for the Macrophage Galactose-type Lectin in Pulmonary Immunity to Mycobacterium tuberculosis

Abstract

Abstract Pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is characterized by inflammatory pathology that is regulated by poorly understood mechanisms of innate immunity. Pattern recognition receptors (PRR) expressed on the surface of macrophages regulate the balance of inflammatory and antimicrobial functions that determine disease outcome. Our work identifies a novel role for the C-type lectin receptor Macrophage Galactose-type Lectin (MGL) PRR in a murine model of experimental tuberculosis. Bone marrow derived macrophages (BMDM) upregulate MGL-1, but not MGL-2, following in vitro exposure to both heat killed and live Mtb. Macrophages from MGL-1-deficient mice display greater lipid accumulation, and increased production of pro-inflammatory cytokines (IL-1b, IL-6 and IFN-g). Mtb growth is also increased in MGL−/− BMDM, independent of the inflammatory outcomes and production of reactive nitrogen species. TB in mice lacking MGL-1 results in increased pro-inflammatory cytokines, more diffuse granulomatous inflammation, and increased accumulation of foamy macrophages. Assessment of disease kinetics suggests that MGL has an important role for controlling mycobacterial burden during the establishment stages of TB disease, and has less influence once the chronic disease stage is established. Macrophages in murine and human TB granulomas contain abundant MGL associated with inflammatory foci. These results suggest that MGL is a potential new therapeutic target against TB.