synergistic tlr26 and tlr9 activation protects mice against lethal influenza pneumonia协同tlr26和tlr9识别激活能保护小鼠免受致命的流感肺炎.pdfVIP

Synergistic TLR2/6 and TLR9 Activation Protects Mice against Lethal Influenza Pneumonia 1,2 3 1,2 1,2 Michael J. Tuvim , Brian E. Gilbert , Burton F. Dickey , Scott E. Evans * 1 Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America, 2 Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas AM Health Science Center, Houston, Texas, United States of America, 3 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America Abstract Lower respiratory tract infections caused by influenza A continue to exact unacceptable worldwide mortality, and recent epidemics have emphasized the importance of preventative and containment strategies. We have previously reported that induction of the lungs’ intrinsic defenses by aerosolized treatments can protect mice against otherwise lethal challenges with influenza A virus. More recently, we identified a combination of Toll like receptor (TLR) agonists that can be aerosolized to protect mice against bacterial pneumonia. Here, we tested whether this combination of synthetic TLR agonists could enhance the survival of mice infected with influenza A/HK/8/68 (H3N2) or A/California/04/2009 (H1N1) influenza A viruses. We report that the TLR treatment enhanced survival whether given before or after the infectious challenge, and that protection tended to correlate with reductions in viral titer 4 d after infection. Surprisingly, protection was not associated with induction of interferon gene expression. Together, these studies suggest that synergistic TLR interactions can protect against influenza virus infectio