Innate immune role for the Macrophage Galactose Lectin (MGL) pathway in pulmonary tuberculosis

Abstract Pulmonary tuberculosis (TB), caused by the pathogen Mycobacterium tuberculosis (Mtb), remains a significant public health threat and accounts for 1.3 million deaths each year. Innate immune responses to Mtb through pathogen recognition receptor signaling are capable of producing protective immune responses and controlling infection. To date, however, an anti-mycobacterial role for the C-type lectin receptor Macrophage Galactose Lectin (MGL), present on the surface of alternatively activated macrophages and dendritic cells, has not been described. MGL has been shown to be an important anti-inflammatory immune receptor during Klebsiella pneumoniae pneumonic sepsis, suggesting its involvement during lung infections; although the role of MGL during TB has not been studied. In preliminary studies, we identified HIV-mediated disruption of MGL gene expression in the lungs of humanized mice co-infected with HIV and Mtb by using a custom macrophage transcriptome array. To further investigate a role for how loss of MGL activation would affect innate immunity to Mtb, we compared disease following pulmonary challenge of MGL−\− and WT mice with Mtb H37Rv. Compared to WT mice, we observed greater mycobacterial burden in the lungs of MGL−\− mice. We additionally observed differences in pulmonary pathology including the accumulation of foamy macrophages and altered patterns of leukocyte organization in granulomas. These data suggest that MGL signaling may regulate myeloid cell antimicrobial activity and inflammatory outcomes at sites of Mtb infection in the lung.