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 journalArticleResearchpeer-review

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 - 1 Jan 2017

Fingerprint

Angiostrongylus cantonensis
Thymus Gland
Atrophy
Stromal Cells
Thymocytes
Antigens
Epithelial Cells
Central Nervous System
Inflammation
Meningoencephalitis
Glucocorticoid Receptors
Meningitis
Immunosuppression
Glucocorticoids
Larva
Anti-Inflammatory Agents
Cell Culture Techniques
Apoptosis
T-Lymphocytes
Injections

Keywords

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

Cite this

Liu, Zhen ; Su, Dong Ming ; Yu, Zi Long ; Wu, Feng ; Liu, Rui Feng ; Luo, Shi Qi ; Lv, Zhi Yue ; Zeng, Xin ; Sun, Xi ; Wu, Zhong Dao. / Soluble antigens from the neurotropic pathogen Angiostrongylus cantonensis directly induce thymus atrophy in a mouse model. In: Oncotarget. 2017 ; Vol. 8, No. 30. pp. 48575-48590.
@article{87e6d2df8d5441cea7be10ca1341281d,
title = "Soluble antigens from the neurotropic pathogen Angiostrongylus cantonensis directly induce thymus atrophy in a mouse model",
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.",
keywords = "Angiostrongylus cantonensis, Central nervous system, Gerotarget, Intrathymic injection, Soluble antigens, Thymic atrophy",
author = "Zhen Liu and Su, {Dong Ming} and Yu, {Zi Long} and Feng Wu and Liu, {Rui Feng} and Luo, {Shi Qi} and Lv, {Zhi Yue} and Xin Zeng and Xi Sun and Wu, {Zhong Dao}",
year = "2017",
month = "1",
day = "1",
doi = "10.18632/oncotarget.17836",
language = "English",
volume = "8",
pages = "48575--48590",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "30",

}

Soluble antigens from the neurotropic pathogen Angiostrongylus cantonensis directly induce thymus atrophy in a mouse model. / Liu, Zhen; Su, Dong Ming; Yu, Zi Long; Wu, Feng; Liu, Rui Feng; Luo, Shi Qi; Lv, Zhi Yue; Zeng, Xin; Sun, Xi; Wu, Zhong Dao.

In: Oncotarget, Vol. 8, No. 30, 01.01.2017, p. 48575-48590.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Soluble antigens from the neurotropic pathogen Angiostrongylus cantonensis directly induce thymus atrophy in a mouse model

AU - Liu, Zhen

AU - Su, Dong Ming

AU - Yu, Zi Long

AU - Wu, Feng

AU - Liu, Rui Feng

AU - Luo, Shi Qi

AU - Lv, Zhi Yue

AU - Zeng, Xin

AU - Sun, Xi

AU - Wu, Zhong Dao

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - Angiostrongylus cantonensis

KW - Central nervous system

KW - Gerotarget

KW - Intrathymic injection

KW - Soluble antigens

KW - Thymic atrophy

UR - http://www.scopus.com/inward/record.url?scp=85025815871&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.17836

DO - 10.18632/oncotarget.17836

M3 - Article

VL - 8

SP - 48575

EP - 48590

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 30

ER -