Pathogen Protection via Toll-like Receptors

Abstract

Mammalian Toll-like receptor (TLR) proteins have evolved to detect a range of molecular cues displayed by pathogens, such as components of bacterial cell walls and viral nucleic acids (see the Perspective by O'Neill). Zhang et al. present evidence for a new member of the mammalian TLR family, TLR11, which plays a role in protecting the urogenital tract from bacterial pathogens. TLR7 and TLR8 have yet to be assigned specific pathogen-derived ligands. Diebold et al. observed recognition of single-stranded RNA (ssRNA) from influenza virus by TLR7 in mice and found that stimulation of this receptor pathway within the endosome of the dendritic cell induced antiviral cytokine expression. Heil et al. also observed guanosine (G)- and uridine (U)-rich ssRNA sequence detection by TLR7 in mouse dendritic cells. However, in human cells, TLR8, rather than TLR7, detected GU-rich ssRNA sequences of human immunodeficiency virus type-1, highlighting a level of divergence in TLR-mediated viral RNA detection between species. L. A. J. O'Neill, After the Toll rush. Science 303 , 1481-1482 (2004). [Summary] [Full Text] D. Zhang, G. Zhang, M. S. Hayden, M. B. Greenblatt, C. Bussey, R. A. Flavell, S. Ghosh, A Toll-like receptor that prevents infection by uropathogenic bacteria. Science 303 , 1522-1526 (2004). [Abstract] [Full Text] S. S. Diebold, T. Kaisho, H. Hemmi, S. Akira, C. Reis e Sousa, Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303 , 1529-1531 (2004). [Abstract] [Full Text] F. Heil, H. Hemmi, H. Hochrein, F. Ampenberger, C. Kirschning, S. Akira, G. Lipford, H. Wagner, S. Bauer, Species-specific recognition of single-stranded RNA via Toll-like receptor 7 and 8. Science 303 , 1526-1529 (2004). [Abstract] [Full Text]