Antiviral immune responses in H5N1-infected human lung tissue and possible mechanisms underlying the hyperproduction of interferon-inducible protein IP-10.
Information on the immune response against H5N1 within the lung is lacking. Here we describe the sustained antiviral immune responses, as indicated by the expression of MxA protein and IFN-alpha mRNA, in autopsy lung tissue from an H5N1-infected patient. H5N1 infection of primary bronchial/tracheal epithelial cells and lung microvascular endothelial cells induced IP-10, and also up-regulated the retinoic acid-inducible gene-I (RIG-I). Down-regulation of RIG-I gene expression decreased IP-10 response. Co-culturing of H5N1-infected pulmonary cells with TNF-alpha led to synergistically enhanced production of IP-10. In the absence of viral infection, TNF-alpha and IFN-alpha also synergistically enhanced IP-10 response. Methylprednisolone showed only a partial inhibitory effect on this chemokine response. Our findings strongly suggest that both the H5N1 virus and the locally produced antiviral cytokines; IFN-alpha and TNF-alpha may have an important role in inducing IP-10 hyperresponse, leading to inflammatory damage in infected lung.
Thitithanyanont
Arunee
A
Faculty of Science, Mahidol University, Bangkok, Thailand.
Engering
Anneke
A
Uiprasertkul
Monkol
M
Ekchariyawat
Peeraya
P
Wiboon-Ut
Suwimon
S
Kraivong
Romchat
R
Limsalakpetch
Amporn
A
Kum-Arb
Utaiwan
U
Yongvanitchit
Kosol
K
Sa-Ard-Iam
Noppadol
N
Rukyen
Pimprapa
P
Mahanonda
Rangsini
R
Kawkitinarong
Kamon
K
Auewarakul
Prasert
P
Utaisincharoen
Pongsak
P
Sirisinha
Stitaya
S
Mason
Carl J
CJ
Fukuda
Mark M
MM
Pichyangkul
Sathit
S
D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000096:biosynthesis; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype; D007251:Influenza, Human / Q000276:immunology*; D016898:Interferon-alpha / Q000096:biosynthesis / Q000494:pharmacology; D008168:Lung / Q000276:immunology* / Q000821:virology*; D008775:Methylprednisolone / Q000494:pharmacology; D064547:Myxovirus Resistance Proteins; D011024:Pneumonia, Viral / Q000276:immunology*; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; C452820:RIGI protein, human; D019204:GTP-Binding Proteins; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D008775:Methylprednisolone