title: Association of TLR3-hyporesponsiveness and functional TLR3 L412F polymorphism with recurrent herpes labialis.
abstract: HSV-1 persistently infects almost 90% of our population; however, only 30% of the infected subjects suffer from recurrent herpes lesions, most frequently herpes labialis (HL). We hypothesized that variations in toll-like receptor (TLR) functions might contribute to HL susceptibility. In our study, the TLR-2/1,-3, and -7/8 responses of immune cell subsets derived from asymptomatic HSV-1 carriers were compared with responses of subjects with HL history. Remarkably, natural killer (NK) cells isolated from HL subjects showed significantly lower IFN-γ responses selectively to the TLR3 agonist poly(I:C). Furthermore, the TLR3 L412F genetic polymorphism was found to reduce NK cell TLR3-responsiveness and is associated with susceptibility to recurrent HL. The TLR3 response detected in HL total peripheral blood mononuclear cells (PBMCs), however, was not impaired, indicating restoration of NK cell TLR3-deficiency through co-stimulatory functions. In conclusion, our results suggest that decreased TLR3 response of NK cells is associated with HL susceptibility; and potentially explain why symptomatic outbreak of HL usually occurs after stress or prolonged UV light exposure, when host co-stimulatory functions are disturbed.
authors.affiliation: Institute of Medical Immunology, Charite-Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany.
authors.forename: Chin-An
authors.initials: CA
authors.lastname: Yang
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Raftery
authors.forename: Lutz
authors.initials: L
authors.lastname: Hamann
authors.forename: Manuel
authors.initials: M
authors.lastname: Guerreiro
authors.forename: Gerald
authors.initials: G
authors.lastname: Grütz
authors.forename: Doreen
authors.initials: D
authors.lastname: Haase
authors.forename: Nadine
authors.initials: N
authors.lastname: Unterwalder
authors.forename: Günther
authors.initials: G
authors.lastname: Schönrich
authors.forename: Ralf R
authors.initials: RR
authors.lastname: Schumann
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Carmen
authors.initials: C
authors.lastname: Scheibenbogen
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D004198:Disease Susceptibility; D006560:Herpes Labialis / Q000235:genetics* / Q000276:immunology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation / Q000187:drug effects; D011070:Poly I-C / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D051196:Toll-Like Receptor 3 / Q000235:genetics* / Q000276:immunology
chemical_list: C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D007371:Interferon-gamma; D011070:Poly I-C