Chi3l3: a potential key orchestrator of eosinophil recruitment in meningitis induced by Angiostrongylus cantonensis

Journal of Neuroinflammation

Feng Wu¹  Datao Lin²  Zilong Yu²  Lifu Wang²  Xi Sun²  Shuo Wan²  Zhongdao Wu²  Zhengyu Li³  Xiaoqiang Sun⁴ 

[1] Department of Clinical Laboratory, the Sixth Affiliated Hospital, Sun Yat-Sen University;Department of Parasitology of Zhongshan School of Medicine, Sun Yat-sen University;Department of neurology, The Second Affiliated Hospital of Nanchang University;Key Laboratory of Tropical Disease Control (SYSU), Ministry of Education;

关键词: Brain;    Eosinophilic infiltration;    Macrophage;    Polarization;    Soluble antigens of A. cantonensis larvae (L4) (sAg);    Chi3l3-IL-13;   

DOI  :  10.1186/s12974-018-1071-2

来源: DOAJ

【 摘 要 】

Abstract Background Angiostrongylus cantonensis, an important foodborne parasite, can induce serious eosinophilic meningitis in non-permissive hosts, such as mouse and human. However, the characteristics and mechanisms of the infection are still poorly understood. This study sought to determine the key molecules and its underlying mechanism in inducing brain eosinophilic infiltration caused by Angiostrongylus cantonensis. Methods Mathematical models were established for prediction of significantly changing genes and the functional associated protein with RNA-seq data in Angiostrongylus cantonensis infection. The expression level of Chi3l3, the predicted key molecule, was verified using Western blotting and real-time quantitative PCR. Critical cell source of Chi3l3 and its relationship with eosinophils were identified with flow cytometry, immunohistochemistry, and further verified by macrophage depletion using liposomal clodronate. The role of soluble antigens of Angiostrongylus cantonensis in eosinophilic response was identified with mice airway allergy model by intranasal administration of Alternaria alternate. The relationship between Chi3l3 and IL-13 was identified with flow cytometry, Western blotting, and Seahorse Bioscience extracellular flux analyzer. Results We analyzed the skewed cytokine pattern in brains of Angiostrongylus cantonensis-infected mice and found Chi3l3 to be an important molecule, which increased sharply during the infection. The percentage of inflammatory macrophages, the main source of Chi3l3, also increased, in line with eosinophils percentage in the brain. Network analysis and mathematical modeling predirect a functional association between Chi3l3 and IL-13. Further experiments verified that the soluble antigen of Angiostrongylus cantonensis induce brain eosinophilic meningitis via aggravating a positive feedback loop between IL-13 and Chi3l3. Conclusions We present evidences in favor of a key role for macrophave-derived Chi3l3 molecule in the infection of Angiostrongylus cantonensis, which aggravates eosinophilic meningitis induced by Angiostrongylus cantonensis via a IL-13-mediated positive feedback loop. These reported results constitute a starting point for future research of angiostrongyliasis pathogenesis and imply that targeting chitinases and chitinase-like-proteins may be clinically beneficial in Angiostrongylus cantonensis-induced eosinophilic meningitis.

【 授权许可】

Unknown