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

Ying Ming Tsai, Shih Chang Hsu, Jian Zhang, Yu Feng Zhou, Beverly Plunkett, Shau Ku Huang, Pei Song Gao

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14 Citations (Scopus)

Abstract

Background:The 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.Methods:Profiling 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.Results:Profiling 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.Conclusion:These 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.

Original languageEnglish
Article numbere64105
JournalPLoS One
Volume8
Issue number5
DOIs
Publication statusPublished - May 29 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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