Receptor for advanced glycation end products is detrimental during influenza A virus pneumonia.
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 RAGE ligand high mobility group box 1 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.
van Zoelen
Marieke A D
MA
Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. M.A.vanZoelen@amc.uva.nl
van der Sluijs
Koenraad F
KF
Achouiti
Ahmed
A
Florquin
Sandrine
S
Braun-Pater
Jennie M
JM
Yang
Huan
H
Nawroth
Peter P
PP
Tracey
Kevin J
KJ
Bierhaus
Angelika
A
van der Poll
Tom
T
D000818:Animals; D042783:Endothelial Cells / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology; D020869:Gene Expression Profiling; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology*; D011014:Pneumonia / Q000276:immunology / Q000473:pathology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000172:deficiency; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology
D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic