Laboratory-based immunology has revealed much about the role of innate immune receptors from insects to mammals, but to what extent do such receptors protect humans from infections? Zhang et al. report a primary human immunodeficiency that points to a dedicated role for a Toll-like receptor (TLR) in protection from infection with a single specific virus, without any apparent influence on other pathogens. Herpes simplex virus (HSV) causes encephalitis in children carrying a mutant allele of TLR3, which normally regulates the antiviral interferon response to virus nucleic acid in the central nervous system and in dendritic cells of the immune system. Maintenance of TLR3 in the innate armory of humans may have been driven by viral infection. These results suggest that other similarly narrow host-pathogen interactions may have also co-evolved.
S.-Y. Zhang, E. Jouanguy, S. Ugolini, A. Smahi, G. Elain, P. Romero, D. Segal, V. Sancho-Shimizu, L. Lorenzo, A. Puel, C. Picard, A. Chapgier, S. Plancoulaine, M. Titeux, C. Cognet, H. von Bernuth, C.-L. Ku, A. Casrouge, X.-X. Zhang, L. Barreiro, J. Leonard, C. Hamilton, P. Lebon, B. Héron, L. Vallée, L. Quintana-Murci, A. Hovnanian, F. Rozenberg, E. Vivier, F. Geissmann, M. Tardieu, L. Abel, J.-L. Casanova, TLR3 deficiency in patients with herpes simplex encephalitis. Science 317, 1522-1527 (2007). [Abstract] [Full Text]