C-X-C motif chemokine ligand 10 produced by mouse Sertoli cells in response to mumps virus infection induces male germ cell apoptosis

Jiang, Qian; Wang, Fei; Shi, Lili; Zhao, Xiang; Gong, Maolei; Liu, Weihua; Song, Chengyi; Li, Qihan; Chen, Yongmei; Wu, Han; Han, Daishu

doi:10.1038/cddis.2017.560

Cited by 25 publications

(26 citation statements)

References 56 publications

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“…Exogenous type I IFN induced ISGs and inhibited MuV replication in Leydig cells, macrophages and Sertoli cells (748), demonstrating effective IFN signaling cascade. MuVexposed Sertoli cells secreted high levels of pro-inflammatory cytokines, among which chemokine (C-X-C motif) ligand 10 (CXCL10) triggered germ cell apoptosis (325), suggesting that Sertoli cells might play a key role in MuV-induced inflammation and germ cell damage in the testis (746). Rat testicular macrophages expressed lower levels of TLR4 receptors than peritoneal macrophages (56) as well as low basal expression of TLR-signaling pathway genes (e.g.…”

Section: Rodent Modelsmentioning

confidence: 99%

“…peritubular cells and extracellular matrix), and degeneration of the germinal epithelium (185). Dysregulation of the testicular cytokinetic microenvironment disrupts both steroidogenesis (271,697,752) and spermatogenesis (53,325,602,681). For instance, during orchitis, infiltrating macrophages and mast cells produce TNF that induces germ cell apoptosis (681), modifies peritubular cell secretions and induces fibrosis (442).…”

Section: Viral Infections and Infertilitymentioning

confidence: 99%

“…high fever; (ii) congestion of the seminiferous tubules caused by the interstitial edema (425); (iii) decreased testosterone production by infected Leydig cells (244); (iv) alteration of the paracrine control of spermatogenesis exerted by somatic cells (Sertoli cells, Leydig cells, testicular macrophages) as a result of their infection; (v) germ cell apoptosis triggered by CXCL10 production by infected Sertoli cells, as observed in the mouse(325).…”

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confidence: 99%

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From Ancient to Emerging Infections: The Odyssey of Viruses in the Male Genital Tract

Tortorec

Matusali

Mahé

et al. 2020

Physiological Reviews

103

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The male genital tract (MGT) is the target of a number of viral infections that can have deleterious consequences at the individual, offspring, and population levels. These consequences include infertility, cancers of male organs, transmission to the embryo/fetal development abnormalities, and sexual dissemination of major viral pathogens such as human immunodeficiency virus (HIV) and hepatitis B virus. Lately, two emerging viruses, Zika and Ebola, have additionally revealed that the human MGT can constitute a reservoir for viruses cleared from peripheral circulation by the immune system, leading to their sexual transmission by cured men. This represents a concern for future epidemics and further underlines the need for a better understanding of the interplay between viruses and the MGT. We review here how viruses, from ancient viruses that integrated the germline during evolution through old viruses (e.g., papillomaviruses originating from Neanderthals) and more modern sexually transmitted infections (e.g., simian zoonotic HIV) to emerging viruses (e.g., Ebola and Zika) take advantage of genital tract colonization for horizontal dissemination, viral persistence, vertical transmission, and endogenization. The MGT immune responses to viruses and the impact of these infections are discussed. We summarize the latest data regarding the sources of viruses in semen and the complex role of this body fluid in sexual transmission. Finally, we introduce key animal findings that are relevant for our understanding of viral infection and persistence in the human MGT and suggest future research directions.

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Section: Rodent Modelsmentioning

confidence: 99%

Section: Viral Infections and Infertilitymentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

From Ancient to Emerging Infections: The Odyssey of Viruses in the Male Genital Tract

Tortorec

Matusali

Mahé

et al. 2020

Physiological Reviews

103

View full text Add to dashboard Cite

show abstract

“…A high level of TNF‐α inhibits testosterone production by Leydig cells (12, 13), and early studies showed that MuV infection impairs the function of Leydig cells (14, 15). In addition, TNF‐α production by Sertoli cells in response to MuV infection can induce male germ cell apoptosis (16). Although Sertoli cells are a major target of MuV infection, the effects of MuV infection on the function of these cells remain unclear.…”

mentioning

confidence: 99%

Mumps virus infection disrupts blood‐testis barrier through the induction of TNF‐α in Sertoli cells

Jiang

Gao

et al. 2019

The FASEB Journal

Self Cite

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Mumps virus (MuV) has high tropism to the testis and may lead to male infertility. Sertoli cells are the major targets of MuV infection. However, the mechanisms by which MuV infection impairs male fertility and Sertoli cell function remain unclear. The present study elucidated the effect of MuV infection on the blood‐testis barrier (BTB). The transepithelial electrical resistance of MuV‐infected mouse Sertoli cells was monitored, and the expression of major proteins of the BTB was examined. We demonstrated that MuV infection disrupted the BTB by reducing the levels of occludin and zonula occludens 1. Sertoli cells derived from Tlr2–/– and Tnfa–/– mice were analyzed for mediating MuV‐induced impairment. TLR2‐mediated TNF‐α production by Sertoli cells in response to MuV infection impaired BTB integrity. MuV‐impaired BTB was not observed in Tlr2–/– and Tnfa–/– Sertoli cells. Moreover, an inhibitor of TNF‐α, pomalidomide, prevents the disruption of BTB in response to MuV infection. FITC‐labeled biotin tracing assay confirmed that BTB permeability and spermatogenesis were transiently impaired by MuV infection in vivo. These findings suggest that the disruption of the BTB could be one of the mechanisms underlying MuV‐impaired male fertility, in which TNF‐α could play a critical role.—Wu, H., Jiang, X., Gao, Y., Liu, W., Wang, F., Gong, M., Chen, R., Yu, X., Zhang, W., Gao, B., Song, C., Han, D. Mumps virus infection disrupts blood‐testis barrier through the induction of TNF‐α in Sertoli cells. FASEB J. 33, 12528–12540 (2019). http://www.fasebj.org

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“…Thus, Sertoli cells can activate a strong innate immune response against ZIKV under laboratory conditions and probably represent a major source of cytokines in infected males. It has been shown that TNF-α increases the production of IP-10 in mouse testis and that this chemokine induced germ cell apoptosis in vivo in Mumps virus-infected testicles [ 94 ]. If a similar mechanism occurs in humans, ZIKV infection could have negative impacts on male fertility altering specific stages of the seminiferous epithelial cycle leading to a decline in total sperm count as has been already reported in long term shedders of this virus in semen [ 55 ].…”

Section: Interactions Of Zikv In the Male Reproductive Tractmentioning

confidence: 99%

Zika Virus Trafficking and Interactions in the Human Male Reproductive Tract

Silva

2018

Pathogens

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Sexual transmission of Zika virus (ZIKV) is a matter of great concern. Infectious viral particles can be shed in semen for as long as six months after infection and can be transferred to male and female sexual partners during unprotected sexual intercourse. The virus can be found inside spermatozoa and could be directly transferred to the oocyte during fertilization. Sexual transmission of ZIKV can contribute to the rise in number of infected individuals in endemic areas as well as in countries where the mosquito vector does not thrive. There is also the possibility, as has been demonstrated in mouse models, that the vaginal deposition of ZIKV particles present in semen could lead to congenital syndrome. In this paper, we review the current literature to understand ZIKV trafficking from the bloodstream to the human male reproductive tract and viral interactions with host cells in interstitial spaces, tubule walls, annexed glands and semen. We hope to highlight gaps to be filled by future research and potential routes for vaccine and antiviral development.

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C-X-C motif chemokine ligand 10 produced by mouse Sertoli cells in response to mumps virus infection induces male germ cell apoptosis

Cited by 25 publications

References 56 publications

From Ancient to Emerging Infections: The Odyssey of Viruses in the Male Genital Tract

From Ancient to Emerging Infections: The Odyssey of Viruses in the Male Genital Tract

Mumps virus infection disrupts blood‐testis barrier through the induction of TNF‐α in Sertoli cells

Zika Virus Trafficking and Interactions in the Human Male Reproductive Tract

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