Sex differences in the response to viral infections: TLR8 and TLR9 ligand stimulation induce higher IL10 production in males

Maria Gabriella Torcia, Lucia Nencioni, Ann Maria Clemente, Livia Civitelli, Ignacio Celestino, Dolores Limongi, Giulia Fadigati, Eloisa Perissi, Federico Cozzolino, Enrico Garaci, Anna Teresa Palamara

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article numbere39853
JournalPLoS One
Issue number6
Publication statusPublished - Jun 29 2012

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)


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