FOR 5644:  The role of immune cells in the function of the normal and diseased testis and epididymis (‘INFINITE’)

• Subject Area: Medicine
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 515636567

Male reproductive disorders are recognized as critical public health issue and increasing global disease burden. Recent studies suggest that sub- or infertility affects up to 12% of men worldwide. Among identifiable and potentially curable causes of male infertility, infections and sterile inflammation of the genital tract have the highest prevalence, between 15-30%. Moreover, the incidence of testicular germ cell tumors is rising worldwide representing the most common cancer in young men. Although evidence exists to support involvement of immune cells in foetal organ development and normal testicular and epididymal function in adults, the role of innate and adaptive immunity in the pathogenesis of male reproductive failure and testis cancer is poorly understood. As the high clinical incidence of leukocyte-associated disorders of testis and epididymis is not reflected by corresponding research activities, we have designed six projects and one (central) Z project that examine the function of immune cells in the testis and epididymis, specifically macrophages, dendritic cells and lymphocytes in terms of organ homeostasis and immunity in normal, aged and diseased conditions. We hypothesize that organ-specific immunity is shaped and controlled by multiple factors, such as cell ontogeny, organ-specific cell composition, niche-specific microenvironment and the gut microbiome. Dramatic changes in the testicular and epididymal immune cell composition during infectious and sterile inflammation, testicular cancer or aging disrupt the organ’s homeostasis. The projects are conceptually integrated and will share technologies, biological materials and expertise. Individual projects will use sophisticated methods such as scRNA-seq analysis, high-dimensional flow cytometry, spatial transcriptomics, CODEX and NicheNet analysis. Projects P1-3 focus on epididymal macrophages (P1), dendritic cells (P2, epididymis and testis) and B cells (P3, epididymis and testis). P1-P3 will comprehensively investigate the immunopathology of acute bacterial epididymo-orchitis and the particular influence of the respective immune cell population. Projects P4-6 will closely focus on the testicular macrophages by investigating the connection of between these cells and the gut microbiome (P4) and aging (P5), respectively, as well as T cells in human testicular cancer and non-neoplastic testicular inflammation (P6). The integrative bioinformatics support provided by the Z project to analyze project-specific datasets (CODEX, scRNA-seq) will strengthen the cooperative nature of this consortium.

• DFG Programme: Research Units
• International Connection: Australia, China

Projects

• Coordination Funds (Applicant Meinhardt, Andreas )
• Deciphering Immune Cell Function in the Testis and Epididymis by Single-Cell Transcriptomics, Spatial Proteomics and Integrative Bioinformatics (Central Project Z1 of the FOR 5644 ‘INFINITE’) (Applicants Bartkuhn, Marek ;  Schlitzer, Andreas ;  Wilhelm, Jochen )
• Deciphering the region-specific distribution and function of dendritic cell populations along the epididymis (Applicants Mayer, Johannes U. ;  Pleuger, Christiane )
• Macrophage dependent inflammation in the ageing testis (Applicants Bhushan, Sudhanshu ;  Schulz, Christian )
• Macrophage-epithelial cell interactions in the epididymis during homeostasis and inflammation (Applicants Meinhardt, Andreas ;  Schlitzer, Andreas )
• Role of regulatory T cells and type 17 T cells in testicular germ cell cancer and testicular inflammation (Applicants Fietz, Daniela ;  Huber, Magdalena ;  Schuppe, Hans-Christian )
• The connection between the gut microbiome and testicular immune cells: implications for testicular diseases (Applicants Bhushan, Sudhanshu ;  Reinhardt, Christoph Ralf )

• Spokesperson: Professor Dr. Andreas Meinhardt