Receptor for advanced glycation end products is detrimental during influenza A virus pneumonia

被引:73
作者
van Zoelen, Marieke A. D. [1 ,2 ]
van der Sluijs, Koenraad F. [1 ,3 ,4 ]
Achouiti, Ahmed [1 ,2 ]
Florquin, Sandrine [5 ]
Braun-Pater, Jennie M. [1 ,2 ]
Yang, Huan [6 ]
Nawroth, Peter P. [7 ]
Tracey, Kevin J. [6 ]
Bierhaus, Angelika [7 ]
van der Poll, Tom [1 ,2 ]
机构
[1] Univ Amsterdam, Acad Med Ctr, Ctr Infect & Immun Amsterdam CINIMA, NL-1105 AZ Amsterdam, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, CEMM, NL-1105 AZ Amsterdam, Netherlands
[3] Univ Amsterdam, Acad Med Ctr, Dept Pulmonol, NL-1105 AZ Amsterdam, Netherlands
[4] Univ Amsterdam, Acad Med Ctr, Dept Expt Immunol, NL-1105 AZ Amsterdam, Netherlands
[5] Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherlands
[6] Feinstein Inst Med Res, Labs Biomed Sci, Manhasset, NY USA
[7] Heidelberg Univ, Dept Internal Med, D-6900 Heidelberg, Germany
关键词
Influenza A virus; Viral pneumonia; Receptor for advanced glycation end products; High mobility group box 1; Host defense; PLASMACYTOID DENDRITIC CELLS; MOBILITY GROUP BOX-1; HOST-DEFENSE; TNF-ALPHA; RAGE; LUNG; MICE; INFECTION; SUPPRESSION; INJURY;
D O I
10.1016/j.virol.2009.05.032
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Pneumonia caused by influenza A virus (IAV) can have devastating effects, resulting in respiratory failure and death. The idea that a new influenza pandemic might occur in the near future has triggered renewed interests in IAV infection. The receptor for advanced glycation end products (RAGE) is expressed on different cell types and plays a key role in diverse inflammatory processes. We here investigated the role of RAGE in the host response to IAV pneumonia using wild-type (wt) and RAGE deficient ((-/-)) mice. Whereas strong RAGE was constitutively expressed in the lungs of uninfected wt mice, in particular on endothelium, IAV pneumonia was associated with enhanced expression on endothelium and de novo expression on bronchial epithelium. Additionally, the high-affinity RACE ligand high mobility group box I was upregulated during IAV pneumonia. RAGE(-/-) mice were relatively protected from IAV induced Mortality and showed an improved Viral clearance and enhanced cellular T cell response and activation of neutrophils. These data Suggest that RAGE is detrimental during IAV pneumonia. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:265 / 273
页数:9
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