Soluble antigens from the neurotropic pathogen Angiostrongylus cantonensis directly induce thymus atrophy in a mouse model

Zhen Liu, Dong Ming Su, Zi Long Yu, Feng Wu, Rui Feng Liu, Shi Qi Luo, Zhi Yue Lv, Xin Zeng, Xi Sun, Zhong Dao Wu

Research output: Contribution to journalArticle

Abstract

The nematode Angiostrongylus cantonensis (A.C.) is a neurotropic pathogen; stage-III larva invade the human (non-permissive host) central nervous system (CNS) to cause eosinophilic meningitis or meningoencephalitis accompanied by immunosuppression. In an A.C.-infected mouse (another non-permissive host) model, CNS damage-associated T cell immune deficiency and severe inflammation were proposed to result from activation of the hypothalamic-pituitary-adrenal (HPA) axis. However, glucocorticoids are anti-inflammatory agents. Additionally, while defects in thymic stromal/epithelial cells (TECs) are the major reason for thymic atrophy, TECs do not express the glucocorticoid receptor. Therefore, activation of the HPA axis cannot fully explain the thymic atrophy and inflammation. Using an A.C.-infected mouse model, we found that A.C.-infected mice developed severe thymic atrophy with dramatic impairments in thymocytes and TECs, particularly cortical TECs, which harbor CD4+CD8+ double-positive thymocytes. The impairments resulted from soluble antigens (sAgs) from A.C. in the thymuses of infected mice, as intrathymic injection of these sAgs into live mice and the addition of these sAgs to thymic cell culture resulted in thymic atrophy and cellular apoptosis, respectively. Therefore, in addition to an indirect effect on thymocytes through the HPA axis, our study reveals a novel mechanism by which A.C. infection in non-permissive hosts directly induces defects in both thymocytes and TECs via soluble antigens.

Original languageEnglish
Pages (from-to)48575-48590
Number of pages16
JournalOncotarget
Volume8
Issue number30
DOIs
StatePublished - 2017

Keywords

  • Angiostrongylus cantonensis
  • Central nervous system
  • Gerotarget
  • Intrathymic injection
  • Soluble antigens
  • Thymic atrophy

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    Liu, Z., Su, D. M., Yu, Z. L., Wu, F., Liu, R. F., Luo, S. Q., Lv, Z. Y., Zeng, X., Sun, X., & Wu, Z. D. (2017). Soluble antigens from the neurotropic pathogen Angiostrongylus cantonensis directly induce thymus atrophy in a mouse model. Oncotarget, 8(30), 48575-48590. https://doi.org/10.18632/oncotarget.17836