TLR3 deficiency - HSE

Stable Identifier
Homo sapiens
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Toll like receptor 3 (TLR3) recognizes double-stranded RNA (dsRNA), an intermediate product during viral replication for most viruses. TLR3 is expressed in various tissues and cells including cells of the central nervous system (CNS) (Bsibsi M et al. 2002). TLR3 activity in neurons and glial cells was found to be critical for controlling herpes simplex virus type 1 (HSV-1) infection in CNS (Lafaille FG et al. 2012). Children with inborn errors of TLR3-mediated immunity are prone to HSV-1 encephalitis (HSE), a rare life-threatening complication during HSV-1 infection (Casrouge A et al. 2006; Perez de Diego R et al. 2010; Zhang SY et al. 2007; Herman M et al. 2012; Lafaille FG et al. 2012). The functional defect in HSE patients with TLR3 deficiency is probably due to impaired induction of type I and III interferon (IFN) by cells of the CNS, which appears to be uniquely dependent upon TLR3 for protection against HSV1 (Zhang SY et al. 2007; Guo Y et al. 2011; Lafaille FG et al. 2012). Importantly, blood cells in the periphery produce normal amounts of interferons, even in TLR3-deficient patients, which perhaps can be explained by RIGI or MDA5-mediated antiviral responses.
Literature References
PubMed ID Title Journal Year
17872438 TLR3 deficiency in patients with herpes simplex encephalitis

Hovnanian, A, Abel, L, Casrouge, A, von Bernuth, H, Lebon, P, Elain, G, Zhang, XX, Vallée, L, Lorenzo, L, Barreiro, L, Leonard, J, Plancoulaine, S, Quintana-Murci, L, Cognet, C, Rozenberg, F, Romero, P, Sancho-Shimizu, V, Smahi, A, Chapgier, A, Geissmann, F, Héron, B, Hamilton, C, Ku, CL, Jouanguy, E, Ugolini, S, Titeux, M, Puel, A, Picard, C, Zhang, SY, Vivier, E, Segal, D, Casanova, JL, Tardieu, M

Science 2007
23622315 Mendelian predisposition to herpes simplex encephalitis

Abel, L, Zhang, SY, Casanova, JL

Handb Clin Neurol 2013
23103873 Impaired intrinsic immunity to HSV-1 in human iPSC-derived TLR3-deficient CNS cells

Abel, L, Ordovas-Montanes, J, Schlaeger, TM, Al-Muhsen, S, Pessach, IM, Abhyankar, A, Herman, M, Elkabetz, Y, Plancoulaine, S, Jouanguy, E, Ciancanelli, MJ, Lafaille, FG, Goldstein, PA, Studer, L, Tu, E, Keros, S, Zhang, SY, Notarangelo, LD, Mostoslavsky, G, Daley, GQ, Ying, SW, Casanova, JL, Tardieu, M

Nature 2012
21911422 Herpes simplex virus encephalitis in a patient with complete TLR3 deficiency: TLR3 is otherwise redundant in protective immunity

Abel, L, Doireau, V, Lebon, P, Lorenzo, L, Plancoulaine, S, Alsina, L, Cardon, A, Rozenberg, F, Sancho-Shimizu, V, Azevedo, J, Ciancanelli, M, Chaussabel, D, Geissmann, F, Philippe, PB, Pérez de Diego, R, Herman, M, Jouanguy, E, Vogt, G, Andrianirina, ZZ, Picard, C, Zhang, SY, Pauwels, E, Anguiano, E, Guo, Y, Audry, M, Casanova, JL, Tardieu, M

J. Exp. Med. 2011
Name Identifier Synonyms
primary immunodeficiency disease DOID:612 immune deficiency disorder, immunodeficiency syndrome, hypoimmunity
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