Origin of testicular macrophages and implication of testicular local microenvironment in metabolically shaping the immunosuppressive phenotype.
Immunology
Final Report Abstract
Macrophages represent a diverse immune cell population with specialized roles in various organs. In the male reproductive system, including the epididymis and testis, macrophages serve as the primary immune cells. However, their origins, diversity, development, and maintenance remain largely unclear. In this study, we identified distinct macrophage populations in the epididymis and testis, each with a unique organ-specific identity. Using a combination of in vivo fate-mapping, chimeric, and parabiotic mouse models alongside detailed cellular analysis, we discovered that these macrophages develop sequentially from yolk sac erythro-myeloid progenitors, embryonic haematopoiesis, and neonatal monocytes. While monocytes are the major developmental source for both epididymal and testicular macrophages, these populations are capable of self-maintenance in steady-state conditions without relying on bone marrow hematopoietic precursors. However, during instances of macrophage depletion (induced by radiation) or infection, bone marrow-derived monocytes are recruited to the epididymis and testis, giving rise to inflammatory macrophages that contribute to tissue damage. Furthermore, we demonstrated that CSF1/CSF1R signalling is critical for the survival of both epididymal and testicular macrophages. These findings reveal the layered ontogeny, maintenance mechanisms, and inflammatory responses of macrophages within the male reproductive organs, shedding light on their essential role in tissue homeostasis and immune responses.
Publications
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Two populations of self-maintaining monocyte-independent macrophages exist in adult epididymis and testis. Proceedings of the National Academy of Sciences, 118(1).
Wang, Ming; Yang, Yalong; Cansever, Dilay; Wang, Yiming; Kantores, Crystal; Messiaen, Sébastien; Moison, Delphine; Livera, Gabriel; Chakarov, Svetoslav; Weinberger, Tobias; Stremmel, Christopher; Fijak, Monika; Klein, Britta; Pleuger, Christiane; Lian, Zhexiong; Ma, Wentao; Liu, Qingzhi; Klee, Kathrin; Händler, Kristian ... & Bhushan, Sudhanshu
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Testicular macrophages: development and function in health and disease. Trends in Immunology, 43(1), 51-62.
Meinhardt, Andreas; Dejucq-Rainsford, Nathalie & Bhushan, Sudhanshu
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Role of macrophage colony stimulating factor and interferon regulatory factor 7 in modulating the immune profile of mouse testicular macrophages. Journal of Reproductive Immunology, 161, 104169.
Yang, Yalong; Kumar, Vishnu; Peng, Wei; Fijak, Monika; Gabriela, Michel; Cai, Wei; Meinhardt, Andreas & Bhushan, Sudhanshu
