Influenza A virus elevates active cathepsin B in primary murine DC

Timo Burster, Thierry Giffon, Martin E Dahl, Pia Björck, Matthew Bogyo, Ekkehard Weber, Kutubuddin Mahmood, David B Lewis, Elizabeth D Mellins

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Dendritic cells (DCs) act as a first-line recognition system for invading pathogens, such as influenza A. The interaction of DC with influenza A virus results in DC activation via endosomal Toll-like receptors and also leads to presentation of viral peptides on MHC class II molecules. Prior work demonstrated that influenza A virus (A/HKx31; H3N2) infection of BALB/c mice activates lung DCs for antigen presentation, and that the enhanced function of these cells persists long after viral clearance and resolution of the virus-induced inflammatory response. Whether influenza A virus has acute or longer-lasting effects on the endo/lysosomal antigen-processing machinery of DCs has not been studied. Here, we show that antigen presentation from intact protein antigen, but not peptide presentation, results in increased T cell stimulation by influenza-exposed lung DCs, suggesting increased antigen processing/loading in these DCs. We find that cathepsin (Cat) B levels and activity are substantially up-regulated in murine lung DCs, harvested 30 days after A/HKx31 infection. CatB levels and activity are also increased in murine splenic and bone marrow-derived DCs, following short-term in vitro exposure to UV-inactivated influenza A virus. Modest effects on CatX are also seen during in vivo and in vitro exposure to influenza A virus. Using a cell permeable Cat inhibitor, we show Cats in influenza-exposed DCs to be functional and required for generation of a T cell epitope from intact ovalbumin. Our findings indicate that influenza A virus affects the MHC class II antigen-processing pathway, an essential pathway for CD4(+) T cell activation.

Original languageEnglish
Pages (from-to)645-55
Number of pages11
JournalInternational Immunology
Volume19
Issue number5
DOIs
Publication statusPublished - May 2007
Externally publishedYes

Keywords

  • Animals
  • Antigen Presentation
  • Bone Marrow Cells
  • Cathepsin B
  • Cells, Cultured
  • Dendritic Cells
  • Influenza A virus
  • Lung
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Spleen
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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  • Cite this

    Burster, T., Giffon, T., Dahl, M. E., Björck, P., Bogyo, M., Weber, E., Mahmood, K., Lewis, D. B., & Mellins, E. D. (2007). Influenza A virus elevates active cathepsin B in primary murine DC. International Immunology, 19(5), 645-55. https://doi.org/10.1093/intimm/dxm030