A dense network of dendritic cells populates the murine epididymis

Silva, Nicolas Da; Cortez-Retamozo, Virna; Reinecker, Hans Christian; Wildgruber, Moritz; Hill, Eric; Brown, Dennis; Świrski, Filip K.; Pittet, Mikaël J.; Breton, Sylvie

doi:10.1530/rep-10-0493

Cited by 105 publications

(205 citation statements)

References 76 publications

(105 reference statements)

Supporting

Mentioning

189

Contrasting

Order By: Relevance

“…A recent study has found a network of dendritic cells in the mouse epididymis (39). These immune cells are thought to constitute the frontline of the epididymal defense against invading microbes (35).…”

Section: Discussionmentioning

confidence: 99%

Pattern Recognition Receptor–Initiated Innate Antiviral Responses in Mouse Epididymal Epithelial Cells

Zhu

Zhao

Liu

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

Viral infections of the epididymis may impair male fertility and spread sexually transmitted pathogens. The innate antiviral immune responses in the epididymis have yet to be intensively investigated. This study found that mouse epididymal epithelial cells (EECs) constitutively express several viral sensors, including TLR3, retinoic acid–inducible gene I, and DNA-dependent activator of IFN regulatory factors. Other DNA sensors, including p204 and cGMP-AMP synthase, can be induced by transfection of synthetic HSV genomic DNA (HSV60). TLR3 and retinoic acid–inducible gene I in EECs can be activated by their common agonist, polyinosinic-polycytidylic acid [poly(I:C)]. The signaling pathway of DNA sensors can be initiated by HSV60. Both poly(I:C) and HSV60 induced the expression of type 1 IFNs and various antiviral proteins, including IFN-stimulated gene 15, 2′,5′-oligoadenylate synthetase, and myxovirus resistance 1. Poly(I:C), but not HSV60, also dramatically induced the expression of major proinflammatory cytokines, including TNF-α and MCP-1, in EECs. In vivo assay confirmed that the local injection of poly(I:C) or HSV60 induced the innate antiviral responses in EECs. This study provided novel insights into the mechanisms underlying the innate antiviral responses in the mouse epididymis.

show abstract

Section: Discussionmentioning

confidence: 99%

Pattern Recognition Receptor–Initiated Innate Antiviral Responses in Mouse Epididymal Epithelial Cells

Zhu

Zhao

Liu

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Cells with dendritic phenotype forming a dense network have been described at the base of the mouse epididymal epithelium, sending cytoplasmic extensions between epithelial cells towards the lumen. 94 NK and NKT cells, innate immune cells participating in the elimination phase of tumour immunoediting, 89 have not been studied in the epididymis, other than in its associated adipose tissue. In contrast to ,2% of all lymphocytes in blood or lymph nodes being NK or NKT cells, these cells account for ,12% in inguinal fat and exceed 30% in the epididymal fat pad.…”

Section: Endogenous Barriers To Tumour Formation: Immunosurveillancementioning

confidence: 99%

Why are epididymal tumours so rare?

Yeung¹,

Wang²,

Cooper³

2012

Asian J Androl

View full text Add to dashboard Cite

Epididymal tumour incidence is at most 0.03% of all male cancers. It is an enigma why the human epididymis does not often succumb to cancer, when it expresses markers of stem and cancer cells, and constitutively expresses oncogenes, pro-proliferative and pro-angiogenic factors that allow tumour cells to escape immunosurveillance in cancer-prone tissues. The privileged position of the human epididymis in evading tumourigenicity is reflected in transgenic mouse models in which induction of tumours in other organs is not accompanied by epididymal neoplasia. The epididymis appears to: (i) prevent tumour initiation (it probably lacks stem cells and has strong anti-oxidative mechanisms, active tumour suppressors and inactive oncogene products); (ii) foster tumour monitoring and destruction (by strong immuno-surveillance and -eradication, and cellular senescence); (iii) avert proliferation and angiogenesis (with persistent tight junctions, the presence of anti-angiogenic factors and misplaced pro-angiogenic factors), which together (iv) promote dormancy and restrict dividing cells to hyperplasia. Epididymal cells may be rendered non-responsive to oncogenic stimuli by the constitutive expression of factors generally inducible in tumours, and resistant to the normal epididymal environment, which mimics that of a tumour niche promoting tumour growth. The threshold for tumour initiation may thus be higher in the epididymis than in other organs. Several anti-tumour mechanisms are those that maintain spermatozoa quiescent and immunologically silent, so the low incidence of cancer in the epididymis may be a consequence of its role in sperm maturation and storage. Understanding these mechanisms may throw light on cancer prevention and therapy in general.

show abstract

“…Our previous work further suggested that the basal compartment of the epithelium might, in fact, be more complex than generally portrayed in the literature. Indeed, using transgenic mouse models expressing fluorescent proteins under the control of the CD11c (integrin alpha X chain) and CX3CR1 (fractalkine receptor), two markers of mononuclear phagocytes (MPs), we described a very abundant and heterogeneous population of immune cells (macrophages and dendritic cells) in the peritubular and interstitial compartments of the mouse epididymis [48]. Owing to the notorious heterogeneity of the MP system and the long-standing controversy that surrounds the respective origin, function, and nomenclature of macrophages and dendritic cells [49][50][51][52][53], we now prefer to use the less restrictive term ''epididymal mononuclear phagocytes'' (eMPs) to describe these cells.…”

Section: Introductionmentioning

confidence: 99%

Epithelial Basal Cells Are Distinct from Dendritic Cells and Macrophages in the Mouse Epididymis1

Shum

Smith

Cortez-Retamozo

et al. 2014

Biology of Reproduction

Self Cite

View full text Add to dashboard Cite

The epithelium that lines the epididymal duct establishes the optimal milieu in which spermatozoa mature, acquire motility, and are stored. This finely tuned environment also protects antigenic sperm against pathogens and autoimmunity, which are potential causes of transient or permanent infertility. The epididymal epithelium is pseudostratified and contains basal cells (BCs) that are located beneath other epithelial cells. Previous studies showed that in the mouse epididymis, BCs possess macrophage-like characteristics. However, we previously identified a dense population of cells belonging to the mononuclear phagocyte (MP) system (comprised of macrophages and dendritic cells) in the basal compartment of the mouse epididymis and showed that a subset of MPs express the macrophage marker F4/80. In the present study, we evaluate the distribution of BCs and MPs in the epididymis of transgenic CD11c-EYFP mice, in which EYFP is expressed exclusively in MPs, using antibodies against the BC marker keratin 5 (KRT5) and the macrophage marker F4/80. Immunofluorescence labeling for laminin, a basement membrane marker, showed that BCs and most MPs are located in the basal region of the epithelium. Confocal microscopy showed that in the initial segment, both BCs and MPs project intraepithelial extensions and establish a very intricate network. Flow cytometry experiments demonstrated that epididymal MPs and BCs are phenotypically distinct. BCs do not express F4/80, and MPs do not express KRT5. Therefore, despite their proximity and some morphological similarities with peritubular macrophages and dendritic cells, BCs do not belong to the MP system.

show abstract

A dense network of dendritic cells populates the murine epididymis

Cited by 105 publications

References 76 publications

Pattern Recognition Receptor–Initiated Innate Antiviral Responses in Mouse Epididymal Epithelial Cells

Pattern Recognition Receptor–Initiated Innate Antiviral Responses in Mouse Epididymal Epithelial Cells

Why are epididymal tumours so rare?

Epithelial Basal Cells Are Distinct from Dendritic Cells and Macrophages in the Mouse Epididymis1

Contact Info

Product

Resources

About