Dataset Information

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-? 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.

SUBMITTER: Torcia MG

PROVIDER: S-EPMC3387221 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

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

Torcia Maria Gabriella MG Nencioni Lucia L Clemente Ann Maria AM Civitelli Livia L Celestino Ignacio I Limongi Dolores D Fadigati Giulia G Perissi Eloisa E Cozzolino Federico F Garaci Enrico E Palamara Anna Teresa AT

PloS one 20120629 6

<h4>Background</h4>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.<h4>Methods</h4>Cytokine production by ...[more]

PMID: 22768144

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Project description:Background and aimsThe topically applied Toll-like receptor 9 [TLR9] agonist cobitolimod is a first-in-class DNA-based oligonucleotide with demonstrated therapeutic efficacy in clinical trials with ulcerative colitis [UC] patients. We here characterized its anti-inflammatory mechanism in UC.MethodsLuminal cobitolimod administration was evaluated in an experimental dextran sodium sulfate [DSS]-induced colitis model. Cultured blood and mucosal cells from UC patients were treated with cobitolimod and analysed via microarray, quantitative real-time PCR, ELISA and flow cytometry. Intestinal slides of cobitolimod-treated UC patients were analysed by immunohistochemistry.ResultsCobitolimod administration markedly suppressed experimental colitis activity, and microarray analyses demonstrated mucosal IL10 upregulation and suppression of IL17 signalling pathways. Cobitolimod treatment was associated with significant induction of mucosal IL10+Tr1 and Treg cells and suppression of Th17 cells. TLR9 knockout mice indicated that cobitolimod requires TLR9 signalling for IL10 induction. In UC patients, mucosal TLR9 levels correlated with severity of inflammation. Cobitolimod inhibited IL17A and IL17F, but increased IL10 and FoxP3 expression in cultured intestinal UC T cells. Cobitolimod-mediated suppression of intestinal IL17+T cells was abrogated by IL10 blockade. Furthermore, cobitolimod led to heightened IL10 production by wound healing macrophages. Immunohistochemistry in intestinal biopsies of cobitolimod-treated UC patients indicated increased presence of IL10+mononuclear and regulatory T cells, as well as reduction of IL17+cells.ConclusionActivation of TLR9 via cobitolimod might represent a novel therapeutic approach in UC, as it suppresses Th17 cells and induces anti-inflammatory IL10+macrophages and regulatory T cells, thereby modifying the dysregulated intestinal cytokine balance.PodcastThis article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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