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NOD-like receptors mediated activation of eosinophils interacting with bronchial epithelial cells: a link between innate immunity and allergic asthma

Cellular & Molecular Immunology volume 10, pages 317–329 (2013)Cite this article

Abstract

Key intracytosolic pattern recognition receptors of innate immunity against bacterial infections are nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs). We elucidated the NOD1 and NOD2-mediated activation of human eosinophils, the principal effector cells for allergic inflammation, upon interacting with human bronchial epithelial BEAS-2B cells in allergic asthma. Eosinophils constitutively expressed NOD1,2 but exhibited nonsignificant responses to release chemokines upon the stimulation by NOD1 ligand γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP) and NOD2 ligand muramyl dipeptide (MDP). However, iE-DAP and MDP could significantly upregulate cell surface expression of CD18 and intercellular adhesion molecule (ICAM)-1 on eosinophils and ICAM-1 on BEAS-2B cells, as well as induce chemokines CCL2 and CXCL8 release in the coculture system (all P<0.05). Both eosinophils and BEAS-2B cells were the main source for CXCL8 and CCL2 release in the coculture system upon iE-DAP or MDP stimulation. Direct interaction between eosinophils and BEAS-2B cells is responsible for CCL2 release, and soluble mediators are implicated in CXCL8 release. ERK and NF-κB play regulatory roles for the expression of adhesion molecules and chemokines in coculture. Treatment with NOD1,2 ligand could induce the subepithelial fibrosis and significantly enhance the serum concentration of total IgE, chemokine CCL5 for eosinophils and T helper type 2 (Th2) cells and asthma Th2 cytokine IL-13 in bronchoalveolar lavage fluid of ovalbumin-sensitized allergic asthmatic mice (all P<0.05). This study provides further evidence of bacterial infection-mediated activation of NOD1,2 in triggering allergic asthma via the activation of eosinophils interacting with bronchial epithelial cells at inflammatory airway.

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Acknowledgements

This work was supported by the Research Grant Committee General Research Fund, Hong Kong (project reference no.: CUHK 476411, principal investigator: CKW) and direct grant from The Chinese University of Hong Kong (reference no.: 2008.1.018).

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Author notes

  1. Chun Kwok Wong and Shuiqing Hu: These authors contributed equally to this work.

  2. Professor CK Wong, Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China. E-mail: ck-wong@cuhk.edu.hk

Authors and Affiliations

  1. Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China

    Chun Kwok Wong, Shuiqing Hu, Karen Ming-Lam Leung, Jie Dong, Huai-Na Qiu, Kelly Yan-Ping Liu & Christopher Wai-Kei Lam

  2. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China

    Lan He, Yi Jun Chu & Ida Miu-Ting Chu

  3. Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau, China

    Christopher Wai-Kei Lam

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Wong, C., Hu, S., Leung, KL. et al. NOD-like receptors mediated activation of eosinophils interacting with bronchial epithelial cells: a link between innate immunity and allergic asthma. Cell Mol Immunol 10, 317–329 (2013). https://doi.org/10.1038/cmi.2012.77

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