Description
Macrophage Galactose-type Lectin Regulates Inflammation and Anti-Microbial Activity of Macrophages in Immunity to Mycobacterium tuberculosis
K.F. Naqvi1, M.B. Huante1, T.B. Saito2,3, M.A. Endsley1, B. B. Gelman2 and J.J. Endsley1
1- Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX
2- Department of Pathology, University of Texas Medical Branch, Galveston, TX
3- Now affiliated with the Vector-Pathogen-Host Interaction Unit, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana
As the global burden of tuberculosis (TB) continues to rise, advances in preventative strategies rely on a deeper understanding of immunomodulatory mechanisms driving inflammation. Inflammatory pathology associated with TB is largely dictated by the innate immune system following contact with Mycobacterium tuberculosis (Mtb). Macrophage pattern recognition receptors, including TLR, NLR, and C-type lectin receptors (CLR), regulate an intricate balance of inflammatory and antimicrobial function, which can determine disease outcome. Although the function of many CLRs in the immune response to Mtb have been defined, a role for the Macrophage Galactose-type Lectin (MGL) receptor remains unknown. Our work identifies a novel role for murine MGL-1 in regulating inflammatory responses and mycobacterial growth in a model of experimental tuberculosis. We observed that murine bone marrow derived macrophages (BMDM) increase MGL-1 transcription and protein production following exposure to both heat killed and live Mtb. Consistent with the immune regulatory function described for MGL, macrophages from MGL-1-deficient mice display increased production of pro-inflammatory cytokines (IL-1b, IL-6 and IFN-g) beginning 12 hours through 72 hours post-Mtb infection. A surprising finding was that Mtb growth increased in MGL-/- BMDM as compared to WT littermate controls. The reduced antimycobacterial activity of MGL-/- BMDM occurred subsequent to pro-inflammatory responses and were independent of changes in nitric oxide or phagocytosis. In support of the in vitro findings, Mtb-infected mice lacking MGL-1 presented with increased pulmonary bacterial burden, greater production of pro-inflammatory cytokines, and accumulation of lipid-rich cells within inflammatory lesions. Collectively, these results identify MGL-1 as an important host receptor for Mtb immunity and a potential target for host-directed therapies intended to reduce inflammatory pathology or limit bacterial proliferation.
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