PMID- 17446210
OWN - NLM
STAT- MEDLINE
DCOM- 20070828
LR  - 20220408
IS  - 0953-8178 (Print)
IS  - 0953-8178 (Linking)
VI  - 19
IP  - 5
DP  - 2007 May
TI  - Influenza A virus elevates active cathepsin B in primary murine DC.
PG  - 645-55
AB  - 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.
FAU - Burster, Timo
AU  - Burster T
AD  - Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 
      94305, USA.
FAU - Giffon, Thierry
AU  - Giffon T
FAU - Dahl, Martin E
AU  - Dahl ME
FAU - Bjorck, Pia
AU  - Bjorck P
FAU - Bogyo, Matthew
AU  - Bogyo M
FAU - Weber, Ekkehard
AU  - Weber E
FAU - Mahmood, Kutubuddin
AU  - Mahmood K
FAU - Lewis, David B
AU  - Lewis DB
FAU - Mellins, Elizabeth D
AU  - Mellins ED
LA  - eng
GR  - AI07290-19/AI/NIAID NIH HHS/United States
GR  - U54 AI057229/AI/NIAID NIH HHS/United States
GR  - U54 RR020843/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070419
PL  - England
TA  - Int Immunol
JT  - International immunology
JID - 8916182
RN  - EC 3.4.22.1 (Cathepsin B)
SB  - IM
MH  - Animals
MH  - *Antigen Presentation
MH  - Bone Marrow Cells/*cytology
MH  - Cathepsin B/biosynthesis/*metabolism
MH  - Cells, Cultured
MH  - Dendritic Cells/cytology/*immunology/metabolism/*virology
MH  - Influenza A virus/*immunology/radiation effects
MH  - Lung/cytology/*immunology
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Spleen/cytology
EDAT- 2007/04/21 09:00
MHDA- 2007/08/29 09:00
CRDT- 2007/04/21 09:00
PHST- 2007/04/21 09:00 [pubmed]
PHST- 2007/08/29 09:00 [medline]
PHST- 2007/04/21 09:00 [entrez]
AID - dxm030 [pii]
AID - 10.1093/intimm/dxm030 [doi]
PST - ppublish
SO  - Int Immunol. 2007 May;19(5):645-55. doi: 10.1093/intimm/dxm030. Epub 2007 Apr 19.