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Exploring the role of mononuclear phagocytes in the epididymis.

Da Silva N, Smith TB - Asian J. Androl. (2015 Jul-Aug)

Bottom Line: The discovery of an intricate arrangement of mononuclear phagocytes (MPs) comprising dendritic cells and macrophages in the murine epididymis suggests that we may have underestimated the existence of a sophisticated mucosal immune system in the posttesticular environment.This review consolidates our current knowledge of the physiology of MPs in the steady state epididymis and speculates on possible interactions between auto-antigenic spermatozoa, pathogens and the immune system by drawing on what is known about the immune system in the intestinal mucosa.Ultimately, further investigation will provide valuable information regarding the origins of pathologies arising as a result of autoimmune or inflammatory responses in the epididymis, including epididymitis and infertility.

View Article: PubMed Central - PubMed

Affiliation: Massachusetts General Hospital and Harvard Medical School, Division of Nephrology, Center for Systems Biology, Boston, Massachusetts, USA.

ABSTRACT
The onslaught of foreign antigens carried by spermatozoa into the epididymis, an organ that has not demonstrated immune privilege, a decade or more after the establishment of central immune tolerance presents a unique biological challenge. Historically, the physical confinement of spermatozoa to the epididymal tubule enforced by a tightly interwoven wall of epithelial cells was considered sufficient enough to prevent cross talk between gametes and the immune system and, ultimately, autoimmune destruction. The discovery of an intricate arrangement of mononuclear phagocytes (MPs) comprising dendritic cells and macrophages in the murine epididymis suggests that we may have underestimated the existence of a sophisticated mucosal immune system in the posttesticular environment. This review consolidates our current knowledge of the physiology of MPs in the steady state epididymis and speculates on possible interactions between auto-antigenic spermatozoa, pathogens and the immune system by drawing on what is known about the immune system in the intestinal mucosa. Ultimately, further investigation will provide valuable information regarding the origins of pathologies arising as a result of autoimmune or inflammatory responses in the epididymis, including epididymitis and infertility.

No MeSH data available.


Related in: MedlinePlus

MP and BC response to the loss of luminal factors caused by EDL in the proximal mouse epididymis. In the steady state epididymis (a), CX3CR1+ CD11c+ intraepithelial Mφs (green) and KRT5+ BCs (red) sit in the basal region of the epithelium and occasionally project extensions (arrows) toward the luminal compartment. After 48 h EDL (b), MPs engulf apoptotic cells and debris and exhibit a phagocytic appearance, while BCs are not visibly involved in the apoptotic cell clearance process. Scale bars = 5 μm, L: lumen; MPs: mononuclear phagocytes; Mφs: macrophages; BCs: basal cells; EDL: efferent duct ligation.
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Figure 3: MP and BC response to the loss of luminal factors caused by EDL in the proximal mouse epididymis. In the steady state epididymis (a), CX3CR1+ CD11c+ intraepithelial Mφs (green) and KRT5+ BCs (red) sit in the basal region of the epithelium and occasionally project extensions (arrows) toward the luminal compartment. After 48 h EDL (b), MPs engulf apoptotic cells and debris and exhibit a phagocytic appearance, while BCs are not visibly involved in the apoptotic cell clearance process. Scale bars = 5 μm, L: lumen; MPs: mononuclear phagocytes; Mφs: macrophages; BCs: basal cells; EDL: efferent duct ligation.

Mentions: Efferent duct ligation (EDL) is a simple surgical procedure that provides an interesting opportunity to study apoptotic clearance in the epididymis; by preventing testicular factors from entering the IS, EDL induces a massive yet transient wave of epithelial apoptosis in the proximal epididymis.455657 Smith et al. have recently reported that epididymal intraepithelial CD11c+ CX3CR1+ Mφs respond to EDL by rapidly engulfing apoptotic cells and debris, thus preserving the integrity of the apical tight junction network.58 Contrasting with Mφs, BCs do not seem to be involved in apoptotic cell clearance (Figure 3); however, recent data have demonstrated that the absence of testis-derived luminal factors reduces their projections and furthermore, BCs could play a role in the post-EDL epithelial regeneration.59 While the extreme situation caused by EDL is never encountered in physiological conditions, these results suggest that one of the primary functions of eMPs, and more specifically intraepithelial CX3CR1+ CD11c+ Mφs, is to actively maintain the integrity of the BEB. However, Mφs are much more than the janitors of the epithelium; by engulfing apoptotic cells, intraepithelial Mφs could play an active role in the maintenance of peripheral tolerance to local self-antigens, including antigens displayed on or released by maturing spermatozoa.


Exploring the role of mononuclear phagocytes in the epididymis.

Da Silva N, Smith TB - Asian J. Androl. (2015 Jul-Aug)

MP and BC response to the loss of luminal factors caused by EDL in the proximal mouse epididymis. In the steady state epididymis (a), CX3CR1+ CD11c+ intraepithelial Mφs (green) and KRT5+ BCs (red) sit in the basal region of the epithelium and occasionally project extensions (arrows) toward the luminal compartment. After 48 h EDL (b), MPs engulf apoptotic cells and debris and exhibit a phagocytic appearance, while BCs are not visibly involved in the apoptotic cell clearance process. Scale bars = 5 μm, L: lumen; MPs: mononuclear phagocytes; Mφs: macrophages; BCs: basal cells; EDL: efferent duct ligation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492049&req=5

Figure 3: MP and BC response to the loss of luminal factors caused by EDL in the proximal mouse epididymis. In the steady state epididymis (a), CX3CR1+ CD11c+ intraepithelial Mφs (green) and KRT5+ BCs (red) sit in the basal region of the epithelium and occasionally project extensions (arrows) toward the luminal compartment. After 48 h EDL (b), MPs engulf apoptotic cells and debris and exhibit a phagocytic appearance, while BCs are not visibly involved in the apoptotic cell clearance process. Scale bars = 5 μm, L: lumen; MPs: mononuclear phagocytes; Mφs: macrophages; BCs: basal cells; EDL: efferent duct ligation.
Mentions: Efferent duct ligation (EDL) is a simple surgical procedure that provides an interesting opportunity to study apoptotic clearance in the epididymis; by preventing testicular factors from entering the IS, EDL induces a massive yet transient wave of epithelial apoptosis in the proximal epididymis.455657 Smith et al. have recently reported that epididymal intraepithelial CD11c+ CX3CR1+ Mφs respond to EDL by rapidly engulfing apoptotic cells and debris, thus preserving the integrity of the apical tight junction network.58 Contrasting with Mφs, BCs do not seem to be involved in apoptotic cell clearance (Figure 3); however, recent data have demonstrated that the absence of testis-derived luminal factors reduces their projections and furthermore, BCs could play a role in the post-EDL epithelial regeneration.59 While the extreme situation caused by EDL is never encountered in physiological conditions, these results suggest that one of the primary functions of eMPs, and more specifically intraepithelial CX3CR1+ CD11c+ Mφs, is to actively maintain the integrity of the BEB. However, Mφs are much more than the janitors of the epithelium; by engulfing apoptotic cells, intraepithelial Mφs could play an active role in the maintenance of peripheral tolerance to local self-antigens, including antigens displayed on or released by maturing spermatozoa.

Bottom Line: The discovery of an intricate arrangement of mononuclear phagocytes (MPs) comprising dendritic cells and macrophages in the murine epididymis suggests that we may have underestimated the existence of a sophisticated mucosal immune system in the posttesticular environment.This review consolidates our current knowledge of the physiology of MPs in the steady state epididymis and speculates on possible interactions between auto-antigenic spermatozoa, pathogens and the immune system by drawing on what is known about the immune system in the intestinal mucosa.Ultimately, further investigation will provide valuable information regarding the origins of pathologies arising as a result of autoimmune or inflammatory responses in the epididymis, including epididymitis and infertility.

View Article: PubMed Central - PubMed

Affiliation: Massachusetts General Hospital and Harvard Medical School, Division of Nephrology, Center for Systems Biology, Boston, Massachusetts, USA.

ABSTRACT
The onslaught of foreign antigens carried by spermatozoa into the epididymis, an organ that has not demonstrated immune privilege, a decade or more after the establishment of central immune tolerance presents a unique biological challenge. Historically, the physical confinement of spermatozoa to the epididymal tubule enforced by a tightly interwoven wall of epithelial cells was considered sufficient enough to prevent cross talk between gametes and the immune system and, ultimately, autoimmune destruction. The discovery of an intricate arrangement of mononuclear phagocytes (MPs) comprising dendritic cells and macrophages in the murine epididymis suggests that we may have underestimated the existence of a sophisticated mucosal immune system in the posttesticular environment. This review consolidates our current knowledge of the physiology of MPs in the steady state epididymis and speculates on possible interactions between auto-antigenic spermatozoa, pathogens and the immune system by drawing on what is known about the immune system in the intestinal mucosa. Ultimately, further investigation will provide valuable information regarding the origins of pathologies arising as a result of autoimmune or inflammatory responses in the epididymis, including epididymitis and infertility.

No MeSH data available.


Related in: MedlinePlus