Uropathogenic Escherichia coli Modulates Innate Immunity To Suppress Th1-Mediated Inflammatory Responses during Infectious Epididymitis

Lang, Tali; Hudemann, Christoph; Tchatalbachev, Svetlin; Stammler, Angelika; Michel, Vera; Aslani, Ferial; Bhushan, Sudhanshu; Chakraborty, Trinad; Renz, Harald; Meinhardt, Andreas

doi:10.1128/iai.01373-13

Cited by 19 publications

(17 citation statements)

References 45 publications

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“…In contrast to a study that found high TNF-a in all leukocytospermic patients (Seshadri et al, 2012), a study that investigated uropathogens reported that TNF-a was high only in semen plasma of patients infected with Gram-negative bacteria rather than patients infected with Gram-positive bacteria (Lang et al, 2014). The effect of infection type on the level of seminal plasma cytokines was not investigated in current study.…”

Section: Discussioncontrasting

confidence: 79%

Association between leukocytospermia and semen interleukin‐6 and tumor necrosis factor‐alpha in infertile men

et al. 2018

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Seminal cytokines were previously reported to adversely affect process of spermatogenesis and ultimately induce poor semen quality. However, association between both IL-6 and TNF-α and leukocytospermia was not yet settled. The aim of this study was to evaluate the association between leukocytospermia and levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in semen of infertile men. This cross-sectional study included 100 age-matched (≥18-45 years.) men. Participants were divided into four groups with 25 patients in each group: Group (A) - infertile patients with leukocytospermia and normal other semen parameters; Group (B) - infertile patients with leukocytospermia and abnormal semen parameters; Group (C) - infertile patients with oligospermia and/or asthenospermia and/or teratospermia but with no leukocytospermia; Group (D) - fertile patients with normal semen parameters and without leukocytospermia. All patients were assessed by detailed medical, sexual, fertility history, and complete physical examination. Laboratory assessment included hormonal and semen analysis and assessment of IL-6 and TNF-α in semen plasma. There were significant differences among the study groups regarding total sperm count, sperm concentration, and progressive motility (p < 0.05 for each). There was significant increase in semen WBC counts in groups A and B vs. groups C and D (p = 0.003). There were significant associations between increase levels of WBCs ≥ 5/HPF and decrease levels of total sperm count (p = 0.023), sperm concentration (p = 0.001), and sperm progressive motility (p = 0.02). There were significant upregulations in mean level of IL-6 (p = 0.001) and mean level of TNF-α (p = 0.003) in groups A and B vs. groups C and D. Overall, leukocytospermia is associated with reduction in sperm count, progressive motility and further upregulation of seminal IL-6 and TNF-α. The effect of treatment of leukocytospermia on the level of seminal cytokines is important point of future research.

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Section: Discussioncontrasting

confidence: 79%

Association between leukocytospermia and semen interleukin‐6 and tumor necrosis factor‐alpha in infertile men

et al. 2018

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“…To elucidate whether the UPEC-induced acrosome reaction leads to an activation of endogenous sialidases, initiating a subsequent desialylation of spermatozoa, an established epididymitis mouse model was utilized (25). Histopathology in MassonGoldner-stained epididymis demonstrated fibrotic remodeling and interstitial leukocytic infiltration as the most obvious consequences 3 days post-UPEC infection, as shown previously (Fig.…”

Section: Desialylation Of Spermatozoa and Epithelial Cells Is A Consesupporting

confidence: 67%

“…Together with neutrophils and T cells, their numbers increase strongly in infection (25,38,39). It appears therefore likely that soluble neuraminidases may also detach sialic acid residues from the cell surface of immune cells during infection.…”

Section: Discussionmentioning

confidence: 99%

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Desialylation of Spermatozoa and Epithelial Cell Glycocalyx Is a Consequence of Bacterial Infection of the Epididymis

Khosravi

Michel

Galuska³

et al. 2016

Journal of Biological Chemistry

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Urinary tract infections caused by uropathogenic Escherichia coli (UPEC) pathovars belong to the most frequent infections in humans. In men, pathogens can also spread to the genital tract via the continuous ductal system, eliciting bacterial prostatitis and/or epididymo-orchitis. Antibiotic treatment usually clears pathogens in acute epididymitis; however, the fertility of patients can be permanently impaired. Because a premature acrosome reaction was observed in an UPEC epididymitis mouse model, and sialidases on the sperm surface are considered to be activated via proteases of the acrosome, we aimed to investigate whether alterations of the sialome of epididymal spermatozoa and surrounding epithelial cells occur during UPEC infection. In UPEC-elicited acute epididymitis in mice, a substantial loss of N-acetylneuraminic acid residues was detected in epididymal spermatozoa and epithelial cells using combined laser microdissection/HPLC-ESI-MS analysis. In support, a substantial reduction of sialic acid residues bound to the surface of spermatozoa was documented in men with a recent history of E. coli-associated epididymitis. In vitro, such an UPEC induced N-acetylneuraminic acid release from human spermatozoa was effectively counteracted by a sialidase inhibitor. These findings strongly suggest a substantial remodeling of the glycocalyx of spermatozoa and epididymal epithelial cells by endogenous sialidases after a premature acrosome reaction during acute epididymitis.

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“…14 days after antibiotic treatment [20]. In epididymitis associated with NPEC, semen parameters had recovered to normal after 84 days, in contrast to the permanent impairment seen in UPEC infection [6,21]. Histological examination of tissue obtained from men with chronic epididymitis in this and a previous study point to ductal obstruction as a consequence of epithelial damage and fibrotic remodelling [9].…”

Section: Activin a Induces Fibrotic Transformation In Epididymis Orgamentioning

confidence: 73%

Uropathogenic Escherichia coli causes fibrotic remodelling of the epididymis

Michel

Duan

Stoschek

et al. 2016

The Journal of Pathology

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Despite antibiotic treatment, up to 40% of patients have impaired fertility after epididymitis due to serovars of Escherichia coli, a frequent pathogen. The reasons for infertility are unclear, but it may result from epididymal duct obstruction. To determine whether E. coli infection of the epididymis causes obstruction due to fibrosis, and to identify the key mediators, tissues from patients with epididymitis were assessed. Additionally, epididymitis was induced with uropathogenic E. coli (UPEC) or commensal serovars in wild-type and MyD88(-/-) mice, which are relatively unresponsive to bacterial pathogens. Epididymal organ cultures were treated with activin A and bacteria and their histology and levels of cytokines and fibrosis markers were analysed. Patients with epididymitis showed severe fibrosis of the epididymal duct. In mice, UPEC infection also caused fibrosis and ductal obstruction in the cauda epididymis. Levels of mRNA for fibrotic markers (α-smooth muscle actin, fibronectin) and cytokines (activin A, TNFα, IL-1α, IL-1β, IL-6) and total collagen levels were significantly elevated. This fibrotic response was blunted by the loss of MyD88. Activin A induced fibrosis in cultured epididymis, which was inhibited by the activin-binding protein follistatin. In summary, bacterial epididymitis causes fibrosis and obstruction. The milder tissue damage in Myd88(-/-) UPEC epididymitis highlights the importance of the host response to infection in causing epididymal damage. Elevated levels of activin A in vivo and fibrotic remodelling elicited by activin A in vitro indicate that this cytokine is a potential target for supplementary treatment to antibiotic therapy. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Uropathogenic Escherichia coli Modulates Innate Immunity To Suppress Th1-Mediated Inflammatory Responses during Infectious Epididymitis

Cited by 19 publications

References 45 publications

Association between leukocytospermia and semen interleukin‐6 and tumor necrosis factor‐alpha in infertile men

Association between leukocytospermia and semen interleukin‐6 and tumor necrosis factor‐alpha in infertile men

Desialylation of Spermatozoa and Epithelial Cell Glycocalyx Is a Consequence of Bacterial Infection of the Epididymis

Uropathogenic Escherichia coli causes fibrotic remodelling of the epididymis

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