The TLR4-TRIF pathway protects against H5N1 influenza virus infection.
Prestimulation of the TLR4 pathway with lipopolysaccharide (LPS) protects mice from lethal infection with H5N1 influenza virus. Here, we reveal that the TLR4-TRIF pathway is required for this protective effect by using mice whose TLR4-related molecules were knocked out. Microarray analysis of primary mouse lung culture cells that were LPS pretreated and infected with an H5N1 virus indicated that TLR3 mRNA was upregulated. Primary lung culture cells of TLR3 knockout mice showed no response to LPS pretreatment against H5N1 virus infection, suggesting that TLR3 is also involved in the preventive effect of LPS. Our data suggest that the TLR4-TRIF axis has an important role in stimulating protective innate immunity against H5N1 influenza A virus infection and that TLR3 signaling is involved in this pathway.
Department of Microbiology and Infectious Diseases, Graduate School of Medicine, Kobe University, Kobe, Japan.
Kyoko
K
Shinya
Mutsumi
M
Ito
Akiko
A
Makino
Motoko
M
Tanaka
Kensuke
K
Miyake
Amie J
AJ
Eisfeld
Yoshihiro
Y
Kawaoka
D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007251:Influenza, Human / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*
D033942:Adaptor Proteins, Vesicular Transport; D051197:Toll-Like Receptor 4; C476286:Ticam1 protein, mouse; C493487:Tlr4 protein, mouse