Mannan‐binding lectin reduces CpG DNA‐induced inflammatory cytokine production by human monocytes

Abstract

Mannan-binding lectin (MBL) belongs to the collectin family and functions as an opsonin that can also initiate complement activation. Our previous study showed that MBL serves as a double-stranded RNA binding protein that attenuates polyriboinosinic-polyribocytidylic acid-induced TLR3 activation. Prompted by these findings, in the present study cross-talk between MBL and CpG-DNA-induced TLR9 activation was investigated. Here, it was found that MBL also interacts with the TLR9 agonist, CpG oligodeoxynucleotide (CpG-ODN), in a calcium-dependent manner. Purified MBL protein suppressed activation of nuclear factor-kappa B signaling and subsequent production of proinflammatory cytokines from human monocytes induced by CpG-ODN 2006. These observations indicate that MBL can down-regulate CpG DNA-induced TLR9 activation, emphasizing the importance of understanding the interaction of MBL with TLR agonist in host immune defense.

Mannan-binding lectin deficiency exacerbates sterile liver injury in mice through enhancing hepatic neutrophil recruitment

“…Indeed, MBL directly interacts with several cell surface pattern recognition receptors (e.g., TLRs, MD2, and CD14) and has been shown to alter the function and cytokine production of monocytes, macrophages, and dendritic cells . A number of studies demonstrated that MBL inhibits the production of pro‐inflammatory cytokines by macrophages during innate immune response . In contrast, Ciencewicki et al .…”

Mannan-Binding Lectin Regulates Inflammatory Cytokine Production, Proliferation, and Cytotoxicity of Human Peripheral Natural Killer Cells

“…Cytokine Production in NK Cells. We previously observed that MBL binding reduced the inflammatory response of monocyte and the T cell proliferation [16,21]. Therefore, the observation that MBL binds to NK cells prompted us to investigate the effect of MBL on the NK cell activation.…”

“…In addition, MBL can also modulate the host immune response independent of complement activation. Our previous studies demonstrated that MBL could bind to human monocyte and attenuate inflammatory response [16,17]. Indeed, monocyte-derived DC from individuals with MBL deficiency showed an enhanced proinflammatory cytokine production in response to microbial stimulation [18].…”

Mannan-binding lectin suppresses growth of hepatocellular carcinoma by regulating hepatic stellate cell activation via the ERK/COX-2/PGE2 pathway

“…11 Additionally, our recently studies showed that MBL could exert its immunomodulatory function apart from complement activation. [12][13][14][15] Although most previous studies were focused on the contribution of MBL to infectious diseases and autoimmune diseases, 16 accumulating evidence suggests that MBL is also involved in development of several cancer types. 17 However, the effect of MBL on tumor development, especially its role in the TME remains unclear.…”