Respiratory syncytial virus activates innate immunity through Toll-like receptor 2
Department of Medicine, Division of Infectious Diseases and Immunology; Program in Immunology and Virology
Animals; Bronchoalveolar Lavage Fluid; Dendritic Cells; Humans; *Immunity, Innate; Macrophages, Peritoneal; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils; Respiratory Syncytial Viruses; Toll-Like Receptor 2
Life Sciences | Medicine and Health Sciences
Respiratory syncytial virus (RSV) is a common cause of infection that is associated with a range of respiratory illnesses, from common cold-like symptoms to serious lower respiratory tract illnesses such as pneumonia and bronchiolitis. RSV is the single most important cause of serious lower respiratory tract illness in children <1 year of age. Host innate and acquired immune responses activated following RSV infection have been suspected to contribute to RSV disease. Toll-like receptors>(TLRs) activate innate and acquired immunity and are candidates for playing key roles in the host immune response to RSV. Leukocytes express TLRs, including TLR2, TLR6, TLR3, TLR4, and TLR7, that can interact with RSV and promote immune responses following infection. Using knockout mice, we have demonstrated that TLR2 and TLR6 signaling in leukocytes can activate innate immunity against RSV by promoting tumor necrosis factor alpha, interleukin-6, CCL2 (monocyte chemoattractant protein 1), and CCL5 (RANTES). As previously noted, TLR4 also contributes to cytokine activation (L. M. Haynes, D. D. Moore, E. A. Kurt-Jones, R. W. Finberg, L. J. Anderson, and R. A. Tripp, J. Virol. 75:10730-10737, 2001, and E. A. Kurt-Jones, L. Popova, L. Kwinn, L. M. Haynes, L. P. Jones, R. A. Tripp, E. E. Walsh, M. W. Freeman, D. T. Golenbock, L. J. Anderson, and R. W. Finberg, Nat. Immunol. 1:398-401, 2000). Furthermore, we demonstrated that signals generated following TLR2 and TLR6 activation were important for controlling viral replication in vivo. Additionally, TLR2 interactions with RSV promoted neutrophil migration and dendritic cell activation within the lung. Collectively, these studies indicate that TLR2 is involved in RSV recognition and subsequent innate immune activation.
DOI of Published Version
J Virol. 2009 Feb;83(3):1492-500. Epub 2008 Nov 19. Link to article on publisher's site
Journal of virology
Murawski, Matthew R.; Bowen, Glennice N.; Cerny, Anna M.; Anderson, Larry J.; Haynes, Lia M.; Tripp, Ralph A.; Kurt-Jones, Evelyn A.; and Finberg, Robert W., "Respiratory syncytial virus activates innate immunity through Toll-like receptor 2" (2008). Open Access Articles. 2196.