Semen of HIV-1–Infected Individuals: Local Shedding of Herpesviruses and Reprogrammed Cytokine Network

Lisco, Andrea; Munawwar, Arshi; Introini, Andrea; Vanpouille, Christophe; Saba, Elisa; Feng, Xingmin; Grivel, Jean‐Charles; Singh, Sarman; Margolis, Leonid

doi:10.1093/infdis/jir700

Cited by 75 publications

(96 citation statements)

References 23 publications

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“…Notably, no significant differences were evident in any cytokine between patients and controls. When calculating the cytokine ratio between blood and semen, specific cytokine spectra were obvious, comparable to those reported for HIV patients and controls (Lisco et al, 2012). In addition, no significant correlations between blood levels of IL-6 and IL-10 and respective seminal concentrations were detected.…”

Section: Discussionsupporting

confidence: 72%

Metabolic syndrome and the seminal cytokine network in morbidly obese males

et al. 2016

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SUMMARYGiven the increasing prevalence of metabolic syndrome (MetS) in males of reproductive age, the objective of this prospective casecontrolled study was to investigate the impact of subacute systemic inflammation associated with MetS on seminal cytokines and standard sperm parameters in comparison with healthy men. Between 2011 and 2014, we recruited 27 patients with MetS out of 41 obese patients screened from an internal outpatient clinic. Twenty-seven age-matched healthy controls were enrolled from 54 men requesting vasectomy in a urological outpatient clinic. A multiplex analysis was performed to quantify simultaneously the level of 30 cytokines (Eotaxin, FGF, Fraktalkine, GCSF, GMCSF, Granzyme A, IFN-c, IL-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-17A, IL-21, IP-10, I-TAC, MCP-1, MIG, MIP-1a, MIP-1b, RANTES, TNF-a, and VEGF) in each 50 lL of blood and seminal plasma during the andrological work-up. Semen analysis was performed according to the WHO (Global status report on noncommunicable diseases, 2010) recommendations, including standard sperm parameters as well as peroxidase-positive leukocytes and polymorphonuclear elastase. Blood levels of C-reactive protein, interleukins 6 and 10 were elevated in MetS (p > 0.001). Two-way hierarchical cluster analysis showed characteristic cytokine networks in semen greatly differing from those in blood, but not between MetS and controls. No deterioration of semen analysis was evident in men diagnosed with MetS. Our results suggest that there is no transmission of the systemic inflammation associated with MetS into semen based on cytokine profiles and that MetS does not impair standard semen parameters to a clinically significant extent.

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Section: Discussionsupporting

confidence: 72%

Metabolic syndrome and the seminal cytokine network in morbidly obese males

et al. 2016

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“…28,79,80 Several other immunologic factors are present in semen at remarkably high levels, including IL-7, TGF-b, and prostaglandins of E series (PGE). 76,81,82 These immune mediators have both pro-and antiinflammatory effects. Understanding the interaction of these various immunologic factors contained in seminal plasma with the genital mucosa has important implications for determining the impact of semen on mucosal propensity to HIV-1 infection.…”

Section: Seminal Plasma and Female Genital Tract Immune Responsementioning

confidence: 99%

“…In the seminal plasma of men infected with HIV, upregulation of specific subset of pro-inflammatory factors in the seminal plasma was demonstrated in several studies. 76,82,101 Furthermore, there is increased interaction between individual cytokines, resulting in 'cytokine networks' that may be less able to effectively respond to viral infection due to their heightened correlated activity. 101 In support of this, seminal plasma from HIV-positive men in the acute phase of infection has been reported to contain much higher concentrations of an array of pro-inflammatory cytokines and chemokines, as compared to uninfected or chronically infected samples.…”

Section: Sp Contains Abundant Immunomodulatory Mediatorsmentioning

confidence: 99%

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Role of Semen in Modulating the Female Genital Tract Microenvironment – Implications for HIV Transmission

Doncel

Anderson

Zalenskaya

2014

American J Rep Immunol

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“…Berlier et al described a positive correlation with interleukin (IL)-1b, 15 while Storey et al described a positive correlation with RANTES, 16 and Sheth et al showed positive correlations with IL-6, IL-8, IL-12, and interferon (IFN)-c. 17 Furthermore, Lisco et al recently suggested that HIV-1 infection causes a ''reprogrammed cytokine network'' in the seminal plasma with elevated levels of several proinflammatory cytokines including IL-1a, IL-1b, IL-6, and IL-8, which do not correlate with blood plasma cytokine levels. 18 This suggests that cytokine expression is compartmentalized and that seminal plasma cytokines are likely produced within the male genital tract.…”

Section: Introductionmentioning

confidence: 99%

Seminal Plasma HIV-1 RNA Concentration Is Strongly Associated with Altered Levels of Seminal Plasma Interferon-γ, Interleukin-17, and Interleukin-5

Hoffman

Anton

Baldwin

et al. 2014

AIDS Research and Human Retroviruses

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Seminal plasma HIV-1 RNA level is an important determinant of the risk of HIV-1 sexual transmission. We investigated potential associations between seminal plasma cytokine levels and viral concentration in the seminal plasma of HIV-1-infected men. This was a prospective, observational study of paired blood and semen samples from 18 HIV-1 chronically infected men off antiretroviral therapy. HIV-1 RNA levels and cytokine levels in seminal plasma and blood plasma were measured and analyzed using simple linear regressions to screen for associations between cytokines and seminal plasma HIV-1 levels. Forward stepwise regression was performed to construct the final multivariate model. The median HIV-1 RNA concentrations were 4.42 log 10 copies/ml (IQR 2.98, 4.70) and 2.96 log 10 copies/ml (IQR 2, 4.18) in blood and seminal plasma, respectively. In stepwise multivariate linear regression analysis, blood HIV-1 RNA level ( p < 0.0001) was most strongly associated with seminal plasma HIV-1 RNA level. After controlling for blood HIV-1 RNA level, seminal plasma HIV-1 RNA level was positively associated with interferon (IFN)-c ( p = 0.03) and interleukin (IL)-17 ( p = 0.03) and negatively associated with IL-5 ( p = 0.0007) in seminal plasma. In addition to blood HIV-1 RNA level, cytokine profiles in the male genital tract are associated with HIV-1 RNA levels in semen. The Th1 and Th17 cytokines IFN-c and IL-17 are associated with increased seminal plasma HIV-1 RNA, while the Th2 cytokine IL-5 is associated with decreased seminal plasma HIV-1 RNA. These results support the importance of genital tract immunomodulation in HIV-1 transmission.

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Semen of HIV-1–Infected Individuals: Local Shedding of Herpesviruses and Reprogrammed Cytokine Network

Abstract: HIV-1 infection results in an aberrant production of cytokines and reactivation of EBV and CMV that further changes the seminal cytokine network. The altered seminal milieu in HIV-1 infection may be a determinant of HIV-1 sexual transmission.

Cited by 75 publications

References 23 publications

Metabolic syndrome and the seminal cytokine network in morbidly obese males

Metabolic syndrome and the seminal cytokine network in morbidly obese males

Role of Semen in Modulating the Female Genital Tract Microenvironment – Implications for HIV Transmission

Seminal Plasma HIV-1 RNA Concentration Is Strongly Associated with Altered Levels of Seminal Plasma Interferon-γ, Interleukin-17, and Interleukin-5

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