Echinococcus multilocularis serpin regulates macrophage polarization and reduces gut dysbiosis in colitis

• Published in: Infection and immunity Vol. 92; no. 8; p. e0023224
• Main Authors: Li, Xiaolu, Liu, Yihui, Zou, Yang, Zhang, Jiayun, Wang, Yugui, Ding, Yingying, Shi, Zhiqi, Guo, Xiaola, Zhang, Shaohua, Yin, Hong, Guo, Aijiang, Wang, Shuai
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 13.08.2024
• Subjects: Animals; Colitis - microbiology; Cytokines - metabolism; Dextran Sulfate - toxicity; Disease Models, Animal; Dysbiosis; Echinococcus multilocularis - immunology; Female; Gastrointestinal Microbiome; Helminth Proteins - metabolism; Host Response and Inflammation; Macrophages - immunology; Macrophages - metabolism; Mice; Mice, Inbred C57BL; Parasitology; RAW 264.7 Cells; Serpins - metabolism; Echinococcus multilocularis serpin; macrophages; gut microbiota; inflammatory bowel disease
• ISSN: 0019-9567; 1098-5522; 1098-5522
• DOI: 10.1128/iai.00232-24

Helminths serve as principal regulators in modulating host immune responses, and their excretory-secretory proteins are recognized as potential therapeutic agents for inflammatory bowel disease. Nevertheless, our comprehension of the mechanisms underlying immunoregulation remains restricted. This investigation delves into the immunomodulatory role of a secretory protein serpin ( -serpin), within the larval stage of . Our observations indicate that -serpin effectively alleviates dextran sulfate sodium-induced colitis, yielding a substantial reduction in immunopathology and an augmentation of anti-inflammatory cytokines. Furthermore, this suppressive regulatory effect is concomitant with the reduction of gut microbiota dysbiosis linked to colitis, as evidenced by a marked impediment to the expansion of the pathobiont taxa Enterobacteriaceae. experiments demonstrate that -serpin facilitates the expansion of M2 phenotype macrophages while concurrently diminishing M1 phenotype macrophages, alongside an elevation in anti-inflammatory cytokine levels. Subsequent investigations involving RAW264.7 and bone marrow macrophages reveal that -serpin induces a conversion of M2 macrophage populations from a pro-inflammatory to an anti-inflammatory phenotype through direct inhibition. Adoptive transfer experiments reveal the peritoneal macrophages induced by -serpin alleviate colitis and gut microbiota dysbiosis. In summary, these findings propose that -serpin holds the potential to regulate macrophage polarization and maintain gut microbiota homeostasis in colitis, establishing it as a promising candidate for developing helminth therapy for preventing inflammatory diseases.