IL-4 increases CD21-dependent infection of pulmonary alveolar epithelial type II cells by EBV

Mol Immunol. 2009 May;46(8-9):1905-10. doi: 10.1016/j.molimm.2009.01.002. Epub 2009 Feb 4.

Abstract

EBV infection has been implicated in the pathogenesis of Idiopathic Pulmonary Fibrosis (IPF). Viral infection may occur from the early or late stage in IPF development. Whether alveolar epithelial cells, AECs, normally express EBV main receptor, CD21, remains uncertain. Such situations prompted us to exploit an efficient direct infection system to investigate EBV receptor repertoire in primary human AECs. Using human primary type 2 AECs, which have been grown in basal medium supplemented with 10 ng/ml Keratinocyte Growth Factor, and type 1 AECs, supplemented with Epithelial Growth Factor, both AEC lines express CD21 mRNA and protein with a significant increase in type 2 cells. Type 2 AECs have been exposed to TGFbeta1 and IL-4, whose expression is associated with IPF development. CD21 is highly expressed in type 2 AECs following IL-4 exposure. EBV bound to type 2 AECs membrane increases significantly following pre-treatment with IL-4 (p<0.001) and decreasing antagonizing CD21 receptor (p<0.01). 200 microg/ml G418-mediated selection of EBV-Neomycin resistant infected cells selected IL-4 pre-exposed type 2 AECs. Our study of a viral cell line model provides evidence to suggest that CD21-dependent viral entry plays a crucial role in type 2 AECs, indicative of an IL-4 response EBV infection in IPF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Epithelial Cells / drug effects*
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Epithelial Cells / virology
  • Epstein-Barr Virus Infections / genetics
  • Epstein-Barr Virus Infections / immunology
  • Epstein-Barr Virus Infections / metabolism
  • Epstein-Barr Virus Infections / pathology*
  • Herpesvirus 4, Human / drug effects
  • Herpesvirus 4, Human / physiology*
  • Humans
  • Idiopathic Pulmonary Fibrosis / etiology
  • Idiopathic Pulmonary Fibrosis / immunology
  • Idiopathic Pulmonary Fibrosis / virology
  • Interleukin-4 / pharmacology*
  • Pulmonary Alveoli / drug effects*
  • Pulmonary Alveoli / immunology
  • Pulmonary Alveoli / metabolism
  • Pulmonary Alveoli / virology
  • Receptors, Complement 3d / antagonists & inhibitors
  • Receptors, Complement 3d / genetics
  • Receptors, Complement 3d / metabolism
  • Receptors, Complement 3d / physiology*
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / virology
  • Th2 Cells / metabolism
  • Up-Regulation / drug effects
  • Up-Regulation / immunology
  • Virus Attachment / drug effects

Substances

  • Receptors, Complement 3d
  • Interleukin-4