Ying Feng1, Cunjing Zheng2, Zongpu Zhou3, Huihui Xiong4, Feng Feng5, Fukang Xie6, Zhong-Dao Wu7. 1. Medical School of South China University of Technology, Guangzhou, 510006, China. Electronic address: 1913696917@qq.com. 2. Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. Electronic address: zhengcj@mail2.sysu.edu.cn. 3. Medical School of South China University of Technology, Guangzhou, 510006, China. Electronic address: zzp9463@163.com. 4. Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. Electronic address: 1605008192@qq.com. 5. The Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510080, China. Electronic address: 147372970@qq.com. 6. Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. Electronic address: frankxie2000@yahoo.com. 7. Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China; Key Laboratory of Tropical Disease Control, Ministry of Education, Guangzhou, 510080, China. Electronic address: wuzhd@mail.sysu.edu.cn.
Abstract
BACKGROUND: Angiostrongylus cantonensis (A. cantonensis) is a foodborne parasite that can invade the central nervous system (CNS), resulting in eosinophilic meningitis (EM). However, the mechanism by which A. cantonensis causes eosinophilic infiltration into CNS is not well understood. METHODS: In this study eosinophilic infiltration into the CNS caused by A. cantonensis was assessed based on eosinophil counts and evaluation of interleukin (IL)-5 and -13 levels by real-time PCR in brain of Balb/c mice. The expression and activation of IL-17A, IL17 receptor (IL-17R A), and IL-17RC and the related signaling molecules nuclear factor (NF)-κB1, NF-κB2, NF-κB activator (Act)1, tumor necrosis factor receptor-associated factor (Traf)5, and Traf6 during A. cantonensis infection in brain tissue of Balb/c mice were examined by real-time, western blotting and immunofluroence. A. cantonensis-infected Balb/c mice were treated with IL-17A neutralizing antibody to evaluate the role of IL17A in eosinophil accumulation in the CNS. RESULTS: Our results showed A. cantonensis infection caused eosinophil accumulation and alterations in IL-5 and -13 levels. The expression of IL-17A and -17RA, Act1, and Traf6 but not of IL-17RC and Traf5 was upregulated during infection; this was accompanied by NF-κB1 and -κB2 activation. Importantly, application of IL-17A neutralizing antibody attenuated eosinophil accumulation in CNS and reversed the changes in IL-5 and -13 expression caused by A. cantonensis infection. Additionally, IL-17RA and Traf6 levels decreased, which was accompanied by NF-κB inactivation. CONCLUSION: IL-17A plays an important role in EM caused by A. cantonensis, possibly through activation of NF-κB via the IL-17RA/Traf6 signaling pathway. These findings highlight the potential for using IL-17A neutralizing antibody as a therapeutic strategy for the treatment of EM.
BACKGROUND:Angiostrongylus cantonensis (A. cantonensis) is a foodborne parasite that can invade the central nervous system (CNS), resulting in eosinophilic meningitis (EM). However, the mechanism by which A. cantonensis causes eosinophilic infiltration into CNS is not well understood. METHODS: In this study eosinophilic infiltration into the CNS caused by A. cantonensis was assessed based on eosinophil counts and evaluation of interleukin (IL)-5 and -13 levels by real-time PCR in brain of Balb/c mice. The expression and activation of IL-17A, IL17 receptor (IL-17R A), and IL-17RC and the related signaling molecules nuclear factor (NF)-κB1, NF-κB2, NF-κB activator (Act)1, tumor necrosis factor receptor-associated factor (Traf)5, and Traf6 during A. cantonensis infection in brain tissue of Balb/c mice were examined by real-time, western blotting and immunofluroence. A. cantonensis-infected Balb/c mice were treated with IL-17A neutralizing antibody to evaluate the role of IL17A in eosinophil accumulation in the CNS. RESULTS: Our results showed A. cantonensis infection caused eosinophil accumulation and alterations in IL-5 and -13 levels. The expression of IL-17A and -17RA, Act1, and Traf6 but not of IL-17RC and Traf5 was upregulated during infection; this was accompanied by NF-κB1 and -κB2 activation. Importantly, application of IL-17A neutralizing antibody attenuated eosinophil accumulation in CNS and reversed the changes in IL-5 and -13 expression caused by A. cantonensis infection. Additionally, IL-17RA and Traf6 levels decreased, which was accompanied by NF-κB inactivation. CONCLUSION:IL-17A plays an important role in EM caused by A. cantonensis, possibly through activation of NF-κB via the IL-17RA/Traf6 signaling pathway. These findings highlight the potential for using IL-17A neutralizing antibody as a therapeutic strategy for the treatment of EM.
Authors: Emily Anderson-Baucum; Annie R Piñeros; Abhishek Kulkarni; Bobbie-Jo Webb-Robertson; Bernhard Maier; Ryan M Anderson; Wenting Wu; Sarah A Tersey; Teresa L Mastracci; Isabel Casimiro; Donalyn Scheuner; Thomas O Metz; Ernesto S Nakayasu; Carmella Evans-Molina; Raghavendra G Mirmira Journal: Cell Metab Date: 2021-09-07 Impact factor: 31.373