Gasdermin D in macrophages drives orchitis by regulating inflammation and antigen presentation processes.

Inflammation in the testes induced by infection and autoimmunity contributes significantly to male infertility, a public health issue. Current therapies using antibiotics and broad-spectrum anti-inflammatory drugs are ineffective against non-bacterial orchitis and induce side effects. This highlights the need to explore the pathogenesis of orchitis and develop alternative therapeutic strategies. In this study, we demonstrated that Gasdermin D (GSDMD) was activated in the testes during uropathogenic Escherichia coli (UPEC)-induced acute orchitis, and that GSDMD in macrophages induced inflammation and affected spermatogenesis during acute and chronic orchitis. In testicular macrophages, GSDMD promoted inflammation and antigen presentation, thereby enhancing the T-cell response after orchitis. Furthermore, the pharmacological inhibition of GSDMD alleviated the symptoms of UPEC-induced acute orchitis. Collectively, these findings provide the first demonstration of GSDMD's role in driving orchitis and suggest that GSDMD may be a potential therapeutic target for treating orchitis. © 2024. The Author(s).

Citation

Chunmei Ma, Jiajia Huang, Yuying Jiang, Lu Liu, Na Wang, Shaoqiong Huang, Honghui Li, Xiangyu Zhang, Shuang Wen, Bingwei Wang, Shuo Yang. Gasdermin D in macrophages drives orchitis by regulating inflammation and antigen presentation processes. EMBO molecular medicine. 2024 Feb;16(2):361-385

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PMID: 38177538

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