Region-specific immune responses to autoimmune epididymitis in the murine reproductive tract

Wijayarathna, Rukmali; Pasalic, Alen; Nicolas, Nour; Biniwale, Sneha; Ravinthiran, Rama; Genovese, Rosemary; Muir, Julie A.; Loveland, Kate L; Meinhardt, Andreas; Fijak, Monika; Hedger, Mark P.

doi:10.1007/s00441-020-03215-8

Cited by 16 publications

(27 citation statements)

References 22 publications

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“…The caput epididymidis remains mostly unaffected throughout the course of infection despite the presence of bacteria and the expression of signaling molecules required to sense bacteria and mount inflammatory responses against them [see Region-Specific Immune Responses to LPS-Induced Epididymitis ( 14 , 34 )]. Similar region-specific immune reactions have also been observed in a mouse model of experimental autoimmune epididymo-orchitis ( 35 ).…”

Section: The Epididymal Response To Infection and Inflammationsupporting

confidence: 68%

“…Various in vivo and in vitro models have clearly pointed to striking region-specific differences in the epididymal immune response. The clearest observation is that the cauda epididymidis is much more sensitive to inflammatory-inflicted damage than the caput epididymidis [ Figure 1D ( 14 , 34 , 35 )]. These observations are complemented by data from patients with acute bacterial epididymitis where in most cases the cauda is predominantly impacted, particularly in severe cases when an abscess is diagnosed ( 36 ).…”

Section: The Epididymal Response To Infection and Inflammationmentioning

confidence: 99%

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Differential Immune Response to Infection and Acute Inflammation Along the Epididymis

et al. 2020

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The epididymis is a tubular structure connecting the vas deferens to the testis. This organ consists of three main regions—caput, corpus, and cauda—that face opposing immunological tasks. A means of combating invading pathogens is required in the distally located cauda, where there is a risk of ascending bacterial infections originating from the urethra. Meanwhile, immune tolerance is necessary at the caput, where spermatozoa with immunogenic neo-antigens originate from the testis. Consistently, when challenged with live bacteria or inflammatory stimuli, the cauda elicits a much stronger immune response and inflammatory-inflicted damage than the caput. At the cellular level, a role for diverse and strategically positioned mononuclear phagocytes is emerging. At the mechanistic level, differential expression of immunoprotective and immunomodulatory mediators has been detected between the three main regions of the epididymis. In this review, we summarize the current state of knowledge about region-specific immunological characteristics and unveil possible underlying mechanisms on cellular and molecular levels. Improved understanding of the different immunological microenvironments is the basis for an improved therapy and counseling of patients with epididymal infections.

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Section: The Epididymal Response To Infection and Inflammationsupporting

confidence: 68%

Section: The Epididymal Response To Infection and Inflammationmentioning

confidence: 99%

Differential Immune Response to Infection and Acute Inflammation Along the Epididymis

et al. 2020

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“…Whether the upregulation of S100a9 within the caput directly drives macrophage polarization into an antiinflammatory and immunosuppressive phenotype in a similar fashion as seen in the testis following UPEC infection (Fan et al, 2021) remains elusive and could be addressed in future studies. Thirdly, data from this and other studies using different immune models show a similar regionalized immune response with a predominant reaction in the cauda that were obtained in vivo and ex vivo independent of an ascending infection (Supplemental Figure S2F, (Silva et al, 2018;Wang et al, 2019;Wijayarathna et al, 2020).…”

Section: Discussionsupporting

confidence: 72%

The regional distribution of resident immune cells shapes distinct immunological environments along the murine epididymis

Pleuger

Hoppe

et al. 2022

Preprint

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The epididymis constitutes an important transition zone for post-testicular sperm maturation and storage. As the organ consists of a single convoluted duct, inflammation-associated tissue damage has a severe impact on fertility. In order to clarify the reasons for region-specific differences in the intensity of immune responses observed in a mouse model of acute bacterial epididymitis, we investigated the heterogeneity of resident immune cell populations within the epididymis under physiological conditions by scRNASeq analysis of extravascular CD45+ cells. 12 distinct immune cell subsets were identified, displaying substantial differences in distribution along the epididymis. Several distinct subsets of macrophages constituted the majority of these cells. Crucially, the proximal and distal regions showed striking differences in their immunological landscapes. These findings indicate that resident immune cells are strategically positioned along the epididymal duct, potentially providing different immunological environments required for sperm maturations and elimination of pathogens ascending the urogenital tract.

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“…The infection leads to several inflammatory responses that can cause the deterioration of the seminal epithelium and the consequent formation of fibrosis. In addition to sexually transmitted diseases, infection and the inflammatory response can also be caused by some systemic viral inflammations that by hematogenous spread can cause infection and inflammation in the testes [28][29][30]. Pathogens themselves, their components or inflammatory factors can cause irreparable damage to the testicles and epididymis.…”

Section: Discussionmentioning

confidence: 99%

Leydig Cells in Patients with Non-Obstructive Azoospermia: Do They Really Proliferate?

Hauptman

Himelreich-Perić

Marić

et al. 2021

Life

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Background: Non-obstructive azoospermia (NOA) is a form of male infertility caused by disorders of the testicular parenchyma and impaired spermatogenesis. This study aimed to investigate the nature of Leydig cell changes in patients with NOA, especially whether their actual proliferation occurred. Methods: 48 testicular biopsies from infertile patients with NOA and 24 testicular biopsies originating from azoospermic patients suffering from obstructive azoospermia (OA) were included in the study. Leydig cells and their possible proliferative activity were analysed by immunohistochemistry and morphometry (stereology). Results: Unlike in the OA group, Leydig cells in NOA patients were sometimes organised into larger clusters and displayed an abundant cytoplasm/hypertrophy. Moreover, significant fibrosis of the interstitial compartment was demonstrated in some NOA samples, often accompanied by inflammatory cells. Stereological analysis showed no increase/proliferation of Leydig cells; on the contrary, these cells decreased in number in the NOA group. Conclusions: The decrease in the number of Leydig cells can be explained by previous inflammatory changes within the testicular interstitium and consequent interstitial fibrosis. The interstitial fibrosis might have a deteriorating effect on Leydig cells.

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Region-specific immune responses to autoimmune epididymitis in the murine reproductive tract

Cited by 16 publications

References 22 publications

Differential Immune Response to Infection and Acute Inflammation Along the Epididymis

Differential Immune Response to Infection and Acute Inflammation Along the Epididymis

The regional distribution of resident immune cells shapes distinct immunological environments along the murine epididymis

Leydig Cells in Patients with Non-Obstructive Azoospermia: Do They Really Proliferate?

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