title: NOD-like receptors mediated activation of eosinophils interacting with bronchial epithelial cells: a link between innate immunity and allergic asthma.
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.
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China. ck-wong@cuhk.edu.hk
authors.forename: Chun Kwok
authors.initials: CK
authors.lastname: Wong
authors.forename: Shuiqing
authors.initials: S
authors.lastname: Hu
authors.forename: Karen Ming-Lam
authors.initials: KM
authors.lastname: Leung
authors.forename: Jie
authors.initials: J
authors.lastname: Dong
authors.forename: Lan
authors.initials: L
authors.lastname: He
authors.forename: Yi Jun
authors.initials: YJ
authors.lastname: Chu
authors.forename: Ida Miu-Ting
authors.initials: IM
authors.lastname: Chu
authors.forename: Huai-Na
authors.initials: HN
authors.lastname: Qiu
authors.forename: Kelly Yan-Ping
authors.initials: KY
authors.lastname: Liu
authors.forename: Christopher Wai-Kei
authors.initials: CW
authors.lastname: Lam
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000276:immunology*; D001980:Bronchi / Q000473:pathology; D018821:CD18 Antigens / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication; D002460:Cell Line; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D018920:Coculture Techniques; D003960:Diaminopimelic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D018821:CD18 Antigens; D018925:Chemokines; D018793:Interleukin-13; D016328:NF-kappa B; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D018799:Intercellular Adhesion Molecule-1; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D003960:Diaminopimelic Acid; C034331:N(2)-(gamma-D-glutamyl)-meso-2,2'-diaminopimelic acid; D048049:Extracellular Signal-Regulated MAP Kinases