Mannose-Binding Lectin Blunts Macrophage Polarization and Ameliorates Lupus Nephritis. e62465

• Published in: PloS one Vol. 8; no. 4
• Main Authors: Cai, Yanxing, Zhang, Weijuan, Xiong, Sidong
• Format: Journal Article
• Language: English
• Published: 01-04-2013
• Subjects: Antigen-antibody complexes
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0062465

Background Deficiency in clearance of self nuclear antigens, including DNA, is the hallmark of systemic lupus erythematosus (SLE), a chronic autoimmnue disease characterized by the production of various autoantibodies, immune complex deposition and severe organ damage. Our previous studies revealed that administration of syngeneic BALB/c mice with activated lymphocyte-derived DNA (ALD-DNA) could induce SLE disease. Mannose-binding lectin (MBL), a secreted pattern recognition receptor with binding activity to DNA, has been proved to be a modulator of inflammation, but whether MBL takes responsibility for DNA clearance, modulates the DNA-mediated immune responses, and is involved in the development of DNA-induced SLE disease remain poorly understood. Methodology/Principal Findings The levels of serum MBL significantly decreased in lupus mice induced by ALD-DNA and were negatively correlated with SLE disease. MBL blunted macrophage M2b polarization by inhibiting the MAPK and NF- Kappa B signaling while enhancing the activation of CREB. Furthermore, MBL suppressed the ability of ALD-DNA-stimulated macrophages to polarize T cells toward Th1 cells and Th17 cells. Importantly, MBL supplement in vivo could ameliorate lupus nephritis. Conclusion/Significance These results suggest MBL supplement could alleviate SLE disease and might imply a potential therapeutic strategy for DNA-induced SLE, which would further our understanding of the protective role of MBL in SLE disease.