PMID- 38066526 OWN - NLM STAT- MEDLINE DCOM- 20231216 LR - 20240102 IS - 1756-3305 (Electronic) IS - 1756-3305 (Linking) VI - 16 IP - 1 DP - 2023 Dec 8 TI - Therapeutic effect of Echinococcus granulosus cyst fluid on bacterial sepsis in mice. PG - 450 LID - 10.1186/s13071-023-06021-7 [doi] LID - 450 AB - BACKGROUND: The primary pathophysiological process of sepsis is to stimulate a massive release of inflammatory mediators to trigger systemic inflammatory response syndrome (SIRS), the major cause of multi-organ dysfunction and death. Like other helminths, Echinococcus granulosus induces host immunomodulation. We sought to determine whether E. granulosus cyst fluid (EgCF) displays a therapeutic effect on sepsis-induced inflammation and tissue damage in a mouse model. METHODS: The anti-inflammatory effects of EgCF were determined by in vitro culture with bone marrow-derived macrophages (BMDMs) and in vivo treatment of BALB/C mice with cecal ligation and puncture (CLP)-induced sepsis. The macrophage phenotypes were determined by flow cytometry, and the levels of cytokines in cell supernatants or in sera of mice were measured (ELISA). The therapeutic effect of EgCF on sepsis was evaluated by observing the survival rates of mice for 72 h after CLP, and the pathological injury to the liver, kidney, and lung was measured under a microscope. The expression of TLR-2/MyD88 in tissues was measured by western blot to determine whether TLR-2/MyD88 is involved in the sepsis-induced inflammatory signaling pathway. RESULTS: In vitro culture with BMDMs showed that EgCF promoted macrophage polarization to M2 type and inhibited lipopolysaccharide (LPS)-induced M1 macrophages. EgCF treatment provided significant therapeutic effects on CLP-induced sepsis in mice, with increased survival rates and alleviation of tissue injury. The EgCF conferred therapeutic efficacy was associated with upregulated anti-inflammatory cytokines (IL-10 and TGF-beta) and reduced pro-inflammatory cytokines (TNF-alpha and INF-gamma). Treatment with EgCF induced Arg-1-expressed M2, and inhibited iNOS-expressed M1 macrophages. The expression of TLR-2 and MyD88 in EgCF-treated mice was reduced. CONCLUSIONS: The results demonstrated that EgCF confers a therapeutic effect on sepsis by inhibiting the production of pro-inflammatory cytokines and inducing regulatory cytokines. The anti-inflammatory effect of EgCF is carried out possibly through inducing macrophage polarization from pro-inflammatory M1 to regulatory M2 phenotype to reduce excessive inflammation of sepsis and subsequent multi-organ damage. The role of EgCF in regulating macrophage polarization may be achieved by inhibiting the TLR2/MyD88 signaling pathway. CI - (c) 2023. The Author(s). FAU - Wang, Shuying AU - Wang S AD - First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China. AD - Anhui Key Laboratory of Infection and Immunity of Bengbu Medical College, Bengbu, 233000, China. AD - Department of Pediatrics, Anqing First People's Hospital of Anhui Medical University, Anqing, 246000, China. FAU - Jiang, Donghui AU - Jiang D AD - Department of Critical Care Medicine, Affiliated Hospital of Jiangnan University, Wuxi, 214122, China. FAU - Huang, Feifei AU - Huang F AD - First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China. AD - Anhui Key Laboratory of Infection and Immunity of Bengbu Medical College, Bengbu, 233000, China. FAU - Qian, Yayun AU - Qian Y AD - First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China. AD - Anhui Key Laboratory of Infection and Immunity of Bengbu Medical College, Bengbu, 233000, China. FAU - Qi, Meitao AU - Qi M AD - Department of Pediatrics, Anqing First People's Hospital of Anhui Medical University, Anqing, 246000, China. FAU - Li, Huihui AU - Li H AD - Anhui Key Laboratory of Infection and Immunity of Bengbu Medical College, Bengbu, 233000, China. FAU - Wang, Xiaoli AU - Wang X AD - Anhui Key Laboratory of Infection and Immunity of Bengbu Medical College, Bengbu, 233000, China. FAU - Wang, Zhi AU - Wang Z AD - Anhui Key Laboratory of Infection and Immunity of Bengbu Medical College, Bengbu, 233000, China. FAU - Wang, Kaigui AU - Wang K AD - Anhui Key Laboratory of Infection and Immunity of Bengbu Medical College, Bengbu, 233000, China. FAU - Wang, Yin AU - Wang Y AD - Department of Critical Care Medicine, Affiliated Hospital of Jiangnan University, Wuxi, 214122, China. FAU - Du, Pengfei AU - Du P AD - Department of Critical Care Medicine, Affiliated Hospital of Jiangnan University, Wuxi, 214122, China. FAU - Zhan, Bin AU - Zhan B AD - National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, 77030, USA. FAU - Zhou, Rui AU - Zhou R AD - First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China. FAU - Chu, Liang AU - Chu L AD - Anhui Key Laboratory of Infection and Immunity of Bengbu Medical College, Bengbu, 233000, China. chew8151@163.com. AD - Second Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China. chew8151@163.com. FAU - Yang, Xiaodi AU - Yang X AD - Anhui Key Laboratory of Infection and Immunity of Bengbu Medical College, Bengbu, 233000, China. yxd_qf@163.com. LA - eng GR - Z202114/the Major Projects of Wuxi Municipal Health and Wellness Commission/ GR - by51201306/512 Talents Development Project of Bengbu Medical College/ GR - by51201205/512 Talents Development Project of Bengbu Medical College/ GR - gxyq2021188/the Support Program for Excellent Talents in Higher Educational Institutions in Anhui Province/ GR - AHWJ2021a005/the Key Projects of Scientific Research of Anhui Provincial Health and Wellness Commission/ PT - Journal Article DEP - 20231208 PL - England TA - Parasit Vectors JT - Parasites & vectors JID - 101462774 RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Toll-Like Receptor 2) RN - 0 (Cytokines) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Lipopolysaccharides) SB - IM MH - Mice MH - Animals MH - *Echinococcus granulosus/metabolism MH - Cyst Fluid/metabolism MH - Myeloid Differentiation Factor 88/metabolism MH - Toll-Like Receptor 2/genetics/metabolism MH - Mice, Inbred BALB C MH - Cytokines/metabolism MH - *Sepsis/drug therapy MH - Inflammation/drug therapy MH - Anti-Inflammatory Agents MH - Lipopolysaccharides PMC - PMC10709918 OTO - NOTNLM OT - Cyst fluid OT - Echinococcus granulosus OT - Immunomodulation OT - Macrophage OT - Sepsis COIS- The authors declare that they have no competing interests. EDAT- 2023/12/09 10:42 MHDA- 2023/12/17 13:19 PMCR- 2023/12/08 CRDT- 2023/12/09 00:07 PHST- 2023/08/07 00:00 [received] PHST- 2023/10/18 00:00 [accepted] PHST- 2023/12/17 13:19 [medline] PHST- 2023/12/09 10:42 [pubmed] PHST- 2023/12/09 00:07 [entrez] PHST- 2023/12/08 00:00 [pmc-release] AID - 10.1186/s13071-023-06021-7 [pii] AID - 6021 [pii] AID - 10.1186/s13071-023-06021-7 [doi] PST - epublish SO - Parasit Vectors. 2023 Dec 8;16(1):450. doi: 10.1186/s13071-023-06021-7.