title: Sex differences in the response to viral infections: TLR8 and TLR9 ligand stimulation induce higher IL10 production in males.
abstract: BACKGROUND
  Susceptibility to viral infections as well as their severity are higher in men than in women. Heightened antiviral responses typical of women are effective for rapid virus clearance, but if excessively high or prolonged, can result in chronic/inflammatory pathologies. We investigated whether this variability could be in part attributable to differences in the response to the Toll-Like Receptors (TLR) more involved in the virus recognition.
  
  
  METHODS
  Cytokine production by peripheral blood mononuclear cells (PBMCs) from male and female healthy donors after stimulation with Toll-like receptors (TLR) 3, 7, 8, 9 ligands or with viruses (influenza and Herpes-simplex-1) was evaluated.
  
  
  RESULTS
  Compared to females, PBMCs from males produced not only lower amounts of IFN-α in response to TLR7 ligands but also higher amounts of the immunosuppressive cytokine IL10 after stimulation with TLR8 and TLR9 ligands or viruses. IL10 production after TLR9 ligands or HSV-1 stimulation was significantly related with plasma levels of sex hormones in both groups, whereas no correlation was found in cytokines produced following TLR7 and TLR8 stimulation.
  
  
  CONCLUSIONS
  Given the role of an early production of IL10 by cells of innate immunity in modulating innate and adaptive immune response to viruses, we suggest that sex-related difference in its production following viral nucleic acid stimulation of TLRs may be involved in the sex-related variability in response to viral infections.
authors: Department of Clinical Physiopathology, University of Firenze, Firenze, Italy. g.torcia@dfc.unifi.it
authors: Maria Gabriella
authors: MG
authors: Torcia
authors: Lucia
authors: L
authors: Nencioni
authors: Ann Maria
authors: AM
authors: Clemente
authors: Livia
authors: L
authors: Civitelli
authors: Ignacio
authors: I
authors: Celestino
authors: Dolores
authors: D
authors: Limongi
authors: Giulia
authors: G
authors: Fadigati
authors: Eloisa
authors: E
authors: Perissi
authors: Federico
authors: F
authors: Cozzolino
authors: Enrico
authors: E
authors: Garaci
authors: Anna Teresa
authors: AT
authors: Palamara
mesh_terms: D000328:Adult; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D057809:HEK293 Cells; D018259:Herpesvirus 1, Human / Q000276:immunology; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D016898:Interferon-alpha / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009696:Nucleic Acids / Q000378:metabolism; D012727:Sex Characteristics; D051200:Toll-Like Receptor 8 / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D012739:Gonadal Steroid Hormones; C508609:IL10 protein, human; D016898:Interferon-alpha; D018793:Interleukin-13; D008024:Ligands; D009696:Nucleic Acids; C495349:TLR8 protein, human; C495371:TLR9 protein, human; D051200:Toll-Like Receptor 8; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12