Novel role for macrophage galactose-type lectin-1 to regulate innate immunity against Mycobacterium tuberculosis

Kubra F. Naqvi, Matthew B. Huante, Tais B. Saito, Mark A. Endsley, Benjamin B. Gelman, Janice J. Endsley

Research output: Contribution to journalArticlepeer-review

Abstract

Tuberculosis (TB) caused by infection with Mycobacterium tuberculosis is characterized by inflammatory pathology and poorly understood mechanisms of innate immunity. Pattern recognition receptors, 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 pattern recognition receptor 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 (MGL)-1 in a mouse model (C57BL/6 and MGL-1-/-) of experimental TB. Murine macrophages upregulated MGL-1 following in vitro exposure to M. tuberculosis, whereas MGL+ cells accumulated at sites of mycobacteria-driven inflammation in the lung. Pulmonary macrophages from MGL-1-deficient mice displayed increased production of proinflammatory cytokines (IL-1β, IL-6, and IFN-γ) that were associated with greater lipid accumulation, following M. tuberculosis infection. Surprisingly, for a CLR, we also observed MGL-1-dependent antimycobacterial activity as evidenced by greater M. tuberculosis proliferation in bone marrow-derived macrophages, and the lung, of MGL-1-deficient mice. Differential transcriptome analysis further revealed that loss of MGL-1 perturbs the activation of various genes involved in the regulation of inflammation and lipid metabolism in the setting of M. tuberculosis infection. These results identify MGL-1 signaling as an important mechanism that regulates innate immunity against M. tuberculosis and indicates the potential for the MGL pathway as a novel therapeutic target for anti-TB immunity.

Original languageEnglish (US)
Pages (from-to)221-233
Number of pages13
JournalJournal of Immunology
Volume207
Issue number1
DOIs
StatePublished - Jul 1 2021

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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