Functional Interaction of Cockroach Allergens and Mannose Receptor (CD206) in Human Circulating Fibrocytes

Abstract

BackgroundThe innate pattern recognition C-type-lectin receptors (CLRs), including mannose receptor (MRC1; CD206), have been suggested to functionally interact with allergens and are critical in controlling immune response. Fibrocytes have been considered to play a role in allergic asthma. Here we sought to investigate the functional interaction of cockroach allergens with CD206 in fibrocytes.MethodsProfiling of N-linked glycans from natural purified cockroach allergen Bla g 2 was accomplished by MALDI-MS. The binding activity of cockroach allergens to CD206 was determined by solid-phase binding assays. Levels of CD206 expression on human fibrocytes and CD206 mediated signaling and cytokine production in Bla g 2 treated fibrocytes were determined.ResultsProfiling of N-linked glycans from Bla g 2 revealed a predominance of small, mannose-terminated glycans with and without fucose. Significant binding of Bla g 2 to CD206 was observed, which was inhibited by yeast mannan (a known CD206 ligand), free mannose, and a blocking antibody (anti-hMR). Flow cytometric analyses of human fibrocytes (CD45+ and collagen-1+) showed selective expression of CD206 on fibrocytes. Functionally, a concentration-dependent uptake of FITC labeled Bla g 2 by fibrocytes was observed, but was significantly inhibited by anti-hMR. Bla g 2 can stimulate up-regulation of inflammatory cytokines including TNF-alpha and IL-6 and activation of nuclear factor kappa B (NF-kB/p65), p38 mitogen-activated protein kinase (p38), ERK, and JNK in cultured fibrocytes. This increased secretion of TNF-alpha and IL-6 and activation of NF-kB, ERK, and JNK was significantly inhibited by the addition of either mannan or mannose. Furthermore, Bla g 2 induced increase in TNF-alpha and IL-6 production was also inhibited by the use of NF-kB, ERK, and JNK inhibitors.ConclusionThese results provide evidence supporting the existence of a functional cockroach allergen-CD206 axis in human fibrocytes, suggesting a role for CD206 in regulating allergen induced allergic responses in asthma.

Mesenchymal stem cells promote CD206 expression and phagocytic activity of macrophages through IL-6 in systemic lupus erythematosus

“…Deficient polymorphonuclear cells have been demonstrated to be partly responsible for the susceptibility to infection in SLE [38]. CD206 is not only an important marker of M2 macrophages but also a critical receptor for recognition of pathogens with glycan structures and plays an important role in immune defense [6]. We reasoned that low-level of CD206 in SLE macrophages might contribute to susceptibility to infection in SLE.…”

“…M2 macrophages exhibiting high-levels of interleukin-10 (IL-10) and transforming growth factor β1 (TGFβ1), but low-levels of tumor necrosis factor α (TNFα) and inducible nitric oxide synthase (iNOS), are known for their high-level of CD206 expression and potent immunoregulatory capability. M1 macrophages however participate in the inflammatory response [5,6]. Macrophages also recognize and phagocytize apoptotic cells, which are involved in the homeostasis and tissue repair [4].…”

Extracellular nicotinamide phosphoribosyltransferase (NAMPT) promotes M2 macrophage polarization in chronic lymphocytic leukemia

“…They were also characterized by increased phagocytosis of FITC-conjugated dextran particles ( Figure 6C), which was however independent of CD206, as inferred by using a neutralizing anti-CD206 antibody (supplemental Figure 11). 39 NLC generated in the presence of rNAMPT had a greater ability to sustain leukemic cells ( Figure 6D). Conversely, when autologous T lymphocytes preactivated using anti-CD3 antibody and IL-2 were cultured with NLCs in the presence of rNAMPT, proliferation was markedly suppressed (Figure 6E).…”

“…Where indicated, NLCs were pretreated with neutralizing monoclonal antibody to CD206 (60 minutes, 37°C). 39 Coverslips were stained 40 and analyzed by confocal microscopy.…”

Mannose receptor modulates macrophage polarization and allergic inflammation through miR-511-3p

“…7,8 Our recent study identified a functional interaction between MRC1 and cockroach allergens in fibrocytes. 9 However, the role of MRC1 in cockroach allergen–induced inflammation and its signaling transduction is poorly understood.…”