GSE168486
Novel Role for Macrophage Galactose-type Lectin-1 to Regulate Innate Immunity against Mycobacterium tuberculosis
Tuberculosis (TB) caused by infection with Mycobacterium tuberculosis (Mtb) is characterized by inflammatory pathology and poorly understood mechanisms of innate immunity. Pattern recognition receptors (PRR), expressed on the surface of macrophages, determine the balance of inflammatory and antimicrobial functions that influence disease outcome. Carbohydrate moieties displayed by mycobacteria can serve as PRR ligands for some members of the C-type lectin receptor (CLR) family; interactions that mediate a variety of incompletely understood immune outcomes. This work identifies a novel role for the CLR Macrophage Galactose-type Lectin-1 (MGL-1) in a mouse model of experimental tuberculosis. Murine macrophages upregulated MGL-1 following in vitro exposure to Mtb, while MGL+ cells accumulated at sites of mycobacteria-driven inflammation in the lung. Pulmonary macrophages from MGL-1-deficient mice displayed increased production of pro-inflammatory cytokines (IL-1b, IL-6 and IFN-g) that was associated with greater lipid accumulation, following Mtb infection. Surprisingly for a CLR, we also observed MGL-1-dependent anti-mycobacterial activity as evidenced by greater Mtb proliferation in BMDM, and the lung, of MGL-1 deficient mice. These results identify MGL-1 signaling as an important mechanism that regulates innate immunity against Mtb and indicate potential for the MGL pathway as a novel therapeutic target for anti-TB immunity. Overall design: Next Generation Sequencing of WT (MGL-1+/+) ( n=5) versus MGL-1-/- (n=5) at 2 and 8 weeks post-Mtb infection or uninfected. Sequencing was performed on lung tissue RNA. The strain used for this study is B6.129-Clec10atm1Hed/J from Jackson labs and WT littermates.