A potential link between bacterial pathogens and allergic conjunctivitis by dendritic cells

Exp Eye Res. 2014 Mar;120:118-26. doi: 10.1016/j.exer.2014.01.014. Epub 2014 Jan 29.

Abstract

The association and mechanism of bacteria linking to the allergic inflammation have not been well elucidated. This study was to explore a potential link between bacterial pathogens and allergic conjunctivitis by dendritic cells (DCs). Bone marrow-derived DCs from BALB/c and MyD88 knockout mice were treated with or without bacterial pathogens or thymic stromal lymphopoietin (TSLP). Two murine models of the topical challenge with LPS or flagellin and experimental allergic conjunctivitis (EAC) were used for in vivo study. The mRNA expression was determined by reverse transcription and real time PCR, and protein production was evaluated by ELISA, Western blotting, immunofluorescent staining and flow cytometry. TSLP mRNA and protein were found to be largely induced by DCs challenged with microbial pathogens, highly by lipopolysaccharide (LPS) and flagellin. The expression of MyD88, NFκB1, NFκB2 and RelA accompanied by NFκB p65 nuclear translocation and TSLP induction were significantly stimulated by flagellin, but blocked by TLR5 antibody or NFκB inhibitor in DCs from MyD88(+/+) but not MyD88(-/-) mice. TSLP promoted the expression of CD40, CD80, OX40 ligand (OX40L), IL-13 and CCL17 by DCs. TSLP-producing DCs were identified in vivo in ocular surface conjunctiva and draining cervical lymph nodes from two murine models of topical challenge with LPS or flagellin, and EAC in BALB/c mice. TSLP/TSLPR/OX40L signaling was observed in DCs of EAC mice. Our findings demonstrate that DCs not only respond to TSLP, but also produce TSLP via TLR/MyD88/NFκB pathways in response to bacterial pathogens, suggesting a potential link between bacteria and allergic disease.

Keywords: allergic conjunctivitis; allergy; dendritic cells; innate immunity; mucosal immunology; thymic stromal lymphopoietin; toll-like receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Bone Marrow Cells
  • Cells, Cultured
  • Conjunctivitis, Allergic / chemically induced
  • Conjunctivitis, Allergic / immunology*
  • Conjunctivitis, Allergic / pathology
  • Cytokines / metabolism*
  • Dendritic Cells / drug effects*
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flagellin / pharmacology*
  • Fluorescent Antibody Technique, Indirect
  • Immunity, Innate
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Polysaccharides, Bacterial / pharmacology*
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Stromal Cells
  • Toll-Like Receptors / metabolism

Substances

  • Cytokines
  • Polysaccharides, Bacterial
  • RNA, Messenger
  • Toll-Like Receptors
  • Flagellin
  • thymic stromal lymphopoietin