ILC3 Function as a Double-Edged Sword in EV71 Infection

Enterovirus 71 (EV71) is a common pathogen responsible for hand, foot, and mouth disease (HFMD), leading to severe neurological complications and even death. However, the mechanisms underlying severe EV71-induced disease remain unclear, and no effective specific treatments are available. In this stu...

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Main Authors: Chang Zhang, Linlin Bao, Feifei Qi, Qi Lv, Fengdi Li, Chuan Qin
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/17/2/184
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author Chang Zhang
Linlin Bao
Feifei Qi
Qi Lv
Fengdi Li
Chuan Qin
author_facet Chang Zhang
Linlin Bao
Feifei Qi
Qi Lv
Fengdi Li
Chuan Qin
author_sort Chang Zhang
collection DOAJ
description Enterovirus 71 (EV71) is a common pathogen responsible for hand, foot, and mouth disease (HFMD), leading to severe neurological complications and even death. However, the mechanisms underlying severe EV71-induced disease remain unclear, and no effective specific treatments are available. In this study, we successfully infected mice of different ages using a mouse-adapted EV71 strain, resulting in disease and mortality. We compared immune system responses between infected and uninfected mice of different ages to identify key pathogenic targets during EV71 infection. Our findings revealed that the level of Group 3 Innate Lymphoid Cells (ILC3s) in mice negatively correlated with the severity of disease induced by EV71 infection. We conducted anti-ILC3 cytokine injections and cytokine neutralizing antibody experiments on 14-day-old EV71-infected mice. The results showed that the cytokine IL-17 secreted by ILC3 cells had a mild protective effect, while IL-22 promoted inflammatory responses. Our research demonstrates that ILC3 cells play a dual role in EV71 infection. These findings not only clarify key immune factors in the progression of EV71-induced disease but also provide a promising approach for the early diagnosis and treatment of severe EV71 infections.
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spelling doaj-art-f85bca5c3b0542b79dc8d026e76572f32025-08-20T02:45:42ZengMDPI AGViruses1999-49152025-01-0117218410.3390/v17020184ILC3 Function as a Double-Edged Sword in EV71 InfectionChang Zhang0Linlin Bao1Feifei Qi2Qi Lv3Fengdi Li4Chuan Qin5Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing 100021, ChinaBeijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing 100021, ChinaBeijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing 100021, ChinaBeijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing 100021, ChinaBeijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing 100021, ChinaBeijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing 100021, ChinaEnterovirus 71 (EV71) is a common pathogen responsible for hand, foot, and mouth disease (HFMD), leading to severe neurological complications and even death. However, the mechanisms underlying severe EV71-induced disease remain unclear, and no effective specific treatments are available. In this study, we successfully infected mice of different ages using a mouse-adapted EV71 strain, resulting in disease and mortality. We compared immune system responses between infected and uninfected mice of different ages to identify key pathogenic targets during EV71 infection. Our findings revealed that the level of Group 3 Innate Lymphoid Cells (ILC3s) in mice negatively correlated with the severity of disease induced by EV71 infection. We conducted anti-ILC3 cytokine injections and cytokine neutralizing antibody experiments on 14-day-old EV71-infected mice. The results showed that the cytokine IL-17 secreted by ILC3 cells had a mild protective effect, while IL-22 promoted inflammatory responses. Our research demonstrates that ILC3 cells play a dual role in EV71 infection. These findings not only clarify key immune factors in the progression of EV71-induced disease but also provide a promising approach for the early diagnosis and treatment of severe EV71 infections.https://www.mdpi.com/1999-4915/17/2/184HFMDEV71ILC3IL-17IL-22
spellingShingle Chang Zhang
Linlin Bao
Feifei Qi
Qi Lv
Fengdi Li
Chuan Qin
ILC3 Function as a Double-Edged Sword in EV71 Infection
Viruses
HFMD
EV71
ILC3
IL-17
IL-22
title ILC3 Function as a Double-Edged Sword in EV71 Infection
title_full ILC3 Function as a Double-Edged Sword in EV71 Infection
title_fullStr ILC3 Function as a Double-Edged Sword in EV71 Infection
title_full_unstemmed ILC3 Function as a Double-Edged Sword in EV71 Infection
title_short ILC3 Function as a Double-Edged Sword in EV71 Infection
title_sort ilc3 function as a double edged sword in ev71 infection
topic HFMD
EV71
ILC3
IL-17
IL-22
url https://www.mdpi.com/1999-4915/17/2/184
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AT linlinbao ilc3functionasadoubleedgedswordinev71infection
AT feifeiqi ilc3functionasadoubleedgedswordinev71infection
AT qilv ilc3functionasadoubleedgedswordinev71infection
AT fengdili ilc3functionasadoubleedgedswordinev71infection
AT chuanqin ilc3functionasadoubleedgedswordinev71infection