期刊
FRONTIERS IN IMMUNOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.815936
关键词
Plasmodium; malaria; sporozoites; exo-erythrocytic forms; circumsporozoite protein; IFN-gamma; ATGs; ubiquitination
类别
资金
- National Natural Science Foundation of China [81672053, 81702247]
- State Key Program of the National Natural Science Foundation of China [81830067]
- Miaopu Talent Grant from Army Medical University [2019R057]
This study revealed an unrecognized role of the sporozoite circumsporozoite protein (CSP) in subverting host innate immunity against liver stage malaria parasite. CSP reduced the levels of autophagy-related genes (ATGs) in hepatocytes, attenuating the killing effect of interferon-gamma (IFN-gamma) on exo-erythrocytic forms (EEFs).
Although exo-erythrocytic forms (EEFs) of liver stage malaria parasite in the parasitophorous vacuole (PV) are encountered with robust host innate immunity, EEFs can still survive and successfully complete the infection of hepatocytes, and the underlying mechanism is largely unknown. Here, we showed that sporozoite circumsporozoite protein (CSP) translocated from the parasitophorous vacuole into the hepatocyte cytoplasm significantly mediated the resistance to the killing of EEFs by interferon-gamma (IFN-gamma). Attenuation of IFN-gamma-mediated killing of EEFs by CSP was dependent on its ability to reduce the levels of autophagy-related genes (ATGs) in hepatocytes. The ATGs downregulation occurred through its enhanced ubiquitination mediated by E3 ligase NEDD4, an enzyme that was upregulated by CSP when it translocated from the cytoplasm into the nucleus of hepatocytes via its nuclear localization signal (NLS) domain. Thus, we have revealed an unrecognized role of CSP in subverting host innate immunity and shed new light for a prophylaxis strategy against liver-stage infection.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据