期刊
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcimb.2021.672720
关键词
CX(3)CL1; NK cells; Angiostrongylus cantonensis; infection; brain injury; central nervous system
资金
- National Natural Science Foundation of China [81501371]
- Post doctorate Foundation of China [2019M651963]
- Post doctorate Foundation of Jiangsu Province [2018Z093]
- Jiangsu Provincial Medical Youth Talent of the Project of Invigorating Health Care through Science, Technology and Education [QNRC2016165]
- Foundation of top notch young and middle-aged medical and health talents in Wuxi [BJ2020079]
- National Basic Research Program of China (973 Program) [2010CB530004]
This study revealed that NK cells infiltrate into the CNS in response to A. cantonensis infection, exhibiting enhanced cytotoxicity and increased production of IFN-gamma and TNF-alpha. The up-regulation of CX(3)CL1 was found to recruit NK cells into the CNS, exacerbating brain damage caused by A. cantonensis infection.
Background Angiostrongylus cantonensis (A. cantonensis), is a food-borne zoonotic parasite that can cause central nervous system (CNS) injury characterized by eosinophilic meningitis. However, the pathogenesis of angiostrongylosis remains elusive. Natural killer cells (NK cells) are unique innate lymphocytes important in early defense against pathogens. The aim of this study was to investigate the role of NK cells in A. cantonensis infection and to elucidate the key factors that recruit NK cells into the CNS. Methods Mouse model of A. cantonensis infection was established by intragastric administration of third-stage larvae. The expression of cytokines and chemokines at gene and protein levels was analyzed by qRT-PCR and ELISA. Distribution of NK cells was observed by immunohistochemistry and flow cytometry. NK cell-mediated cytotoxicity against YAC-1 cells was detected by LDH release assay. The ability of NK cells to secrete cytokines was determined by intracellular flow cytometry and ELISA. Depletion and adoptive transfer of NK cells in vivo was induced by tail vein injection of anti-asialo GM1 rabbit serum and purified splenic NK cells, respectively. CX(3)CL1 neutralization experiment was performed by intraperitoneal injection of anti-CX(3)CL1 rat IgG. Results The infiltration of NK cells in the CNS of A. cantonensis-infected mice was observed from 14 dpi and reached the peak on 18 and 22 dpi. Compared with uninfected splenic NK cells, the CNS-infiltrated NK cells of infected mice showed enhanced cytotoxicity and increased IFN-gamma and TNF-alpha production ability. Depletion of NK cells alleviated brain injury, whereas adoptive transfer of NK cells exacerbated brain damage in A. cantonensis-infected mice. The expression of CX(3)CL1 in the brain tissue and its receptor CX(3)CR1 on the CNS-infiltrated NK cells were both elevated after A. cantonensis infection. CX(3)CL1 neutralization reduced the percentage and absolute number of the CNS-infiltrated NK cells and relieved brain damage caused by A. cantonensis infection. Conclusions Our results demonstrate that the up-regulated CX(3)CL1 in the brain tissue recruits NK cells into the CNS and aggravates brain damage caused by A. cantonensis infection. The findings improve the understanding of the pathogenesis of angiostrongyliasis and expand the therapeutic intervention in CNS disease.
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