Sex Differences in the Response to Viral Infections: TLR8 and TLR9 Ligand Stimulation Induce Higher IL10 Production in Males

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

doi:10.1371/journal.pone.0039853

Cited by 129 publications

(122 citation statements)

References 49 publications

(56 reference statements)

Supporting

Mentioning

107

Contrasting

Unclassified

Order By: Relevance

“…Genetic or hormonal differences that influence immune responses and HPV infection may explain the difference between men and women in strength of association of TNF-α and IL-2 with reduced clearance. Sex differences in cellular and humoral immune responses, as well as cytokine activity, have been consistently documented in previous research (16, 41, 42), ( 16 , 41 , 42 ), and findings from several studies suggest that men have weaker immune responses to HPV infection as compared to women. (43) This may due to previous cervical HPV infection prompting a stronger immune response when exposed to oral HPV infection.…”

Section: Discussionsupporting

confidence: 53%

Association of serum cytokines with oral HPV clearance

et al. 2016

View full text Add to dashboard Cite

Background Initial studies suggest higher serum levels of some pro-inflammatory cytokines may be associated with decreased cervical human papillomavirus (HPV) clearance. However, the relationship of cytokines with oral HPV clearance has not been explored. Methods From 2010 to 2014, oral rinse and serum samples were collected semi-annually from 1,601 adults. Oral rinse samples were tested for HPV DNA using PCR. Based on oral HPV results, 931 serum samples were selected for cytokine evaluation to include a roughly equal number of prevalent (n=307), incident (n=313), and no oral HPV infections (n=311). Electrochemiluminescence multiplex assays were used to determine the concentrations of IL-6, IL-8, TNF-α, IFN-γ, IL-1β, IL-2, IL-4, IL-10, IL-12 and IL-13. The relationship between serum cytokine concentrations (categorized into quartiles) and oral HPV clearance was evaluated with Wei-Lin-Weissfeld regression models, adjusting for HPV infection type (prevalent vs. incident), age, HIV status, and CD4 T cell count. Results Higher TNF-α concentration was associated with decreased clearance in men (highest vs. lowest quartile, adjusted hazard ratio [aHR]=0.52, 95% CI=0.34-0.79) and women (aHR=0.76, 95% confidence interval [CI]=0.55-1.04), with stronger associations in men than women (p-interaction=0.049). Higher IL-2 concentration was associated with reduced clearance in men (aHR=0.69, 95% CI=0.50-0.95), but not women (p-interaction=0.058). Results were similar within CD4 T cell strata (CD4 ≥500 or CD4<500 cells/μl) among HIV-infected participants. No other cytokines were associated with clearance. Conclusion High serum TNF-α is associated with reduced clearance of oral HPV infection.

show abstract

Section: Discussionsupporting

confidence: 53%

Association of serum cytokines with oral HPV clearance

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Consistent with our observations, IL-10 levels increase in pregnant women (85, 86) and have been associated with diminished symptoms of RA during pregnancy (87). Even though, to the best of our knowledge, there is no evidence of higher IL-10 baseline levels in males compared to females, upon viral infections males produce substantially higher IL-10 levels (88), which could directly impact neutrophil phenotype and function. Thus, more studies addressing the effects of androgens in the development of LDGs and GR-MDSCs are warranted.…”

Section: Discussionmentioning

confidence: 94%

Multicenter Systems Analysis of Human Blood Reveals Immature Neutrophils in Males and During Pregnancy

Blažková

Gupta

Liu

et al. 2017

The Journal of Immunology

View full text Add to dashboard Cite

Despite clear differences in immune system responses and in the prevalence of autoimmune diseases between males and females, there is little understanding of the processes involved. Here, we identified a gene signature of immature-like neutrophils (Immature-Like Neutrophil Signature, ILNS), characterized by the overexpression of genes encoding for several granule-containing proteins, which was found in higher levels (up to 3-fold) in young (20 – 30 years old) but not older (60 – >89 years old) males compared with females. Functional and phenotypic characterization of peripheral blood neutrophils revealed more mature and responsive neutrophils in young females, which also exhibited an elevated capacity in neutrophil extracellular trap (NET) formation at baseline and upon microbial or sterile autoimmune stimuli. Expression levels of the ILNS increased linearly with pregnancy, an immune state of increased susceptibility to and severity of certain infections. Using mass cytometry, we also find increased frequencies of immature forms of neutrophils in the blood of women in late pregnancy. Thus, our findings show novel sex-differences in innate immunity and identify a common neutrophil signature in males and in pregnant women.

show abstract

“…Such a gender difference in the CHIKV-specific IgG level was found at the baseline and may be due to the natural estrogen-driven shift towards the Th2 cytokine profile for promoting antibody production in women, or to the inhibitory effect of dihydrotestosterone (DHS) on B cell functioning in men [32]. On an other hand, it may also be due to higher production of immunosuppressive IL-10, which has been found to correlate positively with DHS and negatively with serum IgG 3 titres in male patients with other viral infections [33,34]. These same mechanisms may have driven the discrepancy between IgG titres following CHIKV infection in men and women.…”

Section: Discussionmentioning

confidence: 99%

Predictors of Chikungunya rheumatism: a prognostic survey ancillary to the TELECHIK cohort study

et al. 2013

View full text Add to dashboard Cite

IntroductionLong-lasting relapsing or lingering rheumatic musculoskeletal pain (RMSP) is the hallmark of Chikungunya virus (CHIKV) rheumatism (CHIK-R). Little is known on their prognostic factors. The aim of this prognostic study was to search the determinants of lingering or relapsing RMSP indicative of CHIK-R.MethodsThree hundred and forty-six infected adults (age ≥ 15 years) having declared RMSP at disease onset were extracted from the TELECHIK cohort study, Reunion island, and analyzed using a multinomial logistic regression model. We also searched for the predictors of CHIKV-specific IgG titres, assessed at the time of a serosurvey, using multiple linear regression analysis.ResultsOf these, 111 (32.1%) reported relapsing RMSP, 150 (43.3%) lingering RMSP, and 85 (24.6%) had fully recovered (reference group) on average two years after acute infection. In the final model controlling for gender, the determinants of relapsing RMSP were the age 45-59 years (adjusted OR: 2.9, 95% CI: 1.0, 8.6) or greater or equal than 60 years (adjusted OR: 10.4, 95% CI: 3.5, 31.1), severe rheumatic involvement (fever, at least six joints plus four other symptoms) at presentation (adjusted OR: 3.6, 95% CI: 1.5, 8.2), and CHIKV-specific IgG titres (adjusted OR: 3.2, 95% CI: 1.8, 5.5, per one unit increase). Prognostic factors for lingering RMSP were age 45-59 years (adjusted OR: 6.4, 95% CI: 1.8, 22.1) or greater or equal than 60 years (adjusted OR: 22.3, 95% CI: 6.3, 78.1), severe initial rheumatic involvement (adjusted OR: 5.5, 95% CI: 2.2, 13.8) and CHIKV-specific IgG titres (adjusted OR: 6.2, 95% CI: 2.8, 13.2, per one unit increase). CHIKV specific IgG titres were positively correlated with age, female gender and the severity of initial rheumatic symptoms.ConclusionsOur data support the roles of age, severity at presentation and CHIKV specific IgG titres for predicting CHIK-R. By identifying the prognostic value of the humoral immune response of the host, this work also suggest a significant contribution of the adaptive immune response to the physiopathology of CHIK-R and should help to reconsider the paradigm of this chronic infection primarily shifted towards the involvement of the innate immune response.

show abstract

Sex Differences in the Response to Viral Infections: TLR8 and TLR9 Ligand Stimulation Induce Higher IL10 Production in Males

Cited by 129 publications

References 49 publications

Association of serum cytokines with oral HPV clearance

Association of serum cytokines with oral HPV clearance

Multicenter Systems Analysis of Human Blood Reveals Immature Neutrophils in Males and During Pregnancy

Predictors of Chikungunya rheumatism: a prognostic survey ancillary to the TELECHIK cohort study

Contact Info

Product

Resources

About