Low-frequency, exhausted immune status of CD56dim NK cells and disordered inflammatory cytokine secretion of CD56bright NK cells associated with progression of severe HFMD, especially in EV71-infected patients

Pan, Zhaojun; Zhao, Ruqian; Shen, Yanxi; Liu, Kai; Xue, Wei; Liang, Chengfei; Peng, Mingli; Hu, Peng; Chen, Min; Xu, Hongmei

doi:10.1016/j.intimp.2021.108369

Cited by 6 publications

(3 citation statements)

References 43 publications

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“…[19][20][21][22] However, the levels of these factors increased significantly in children with HFMD. [23,24] Therefore, the decreased abundance of Prevotella and Clostridium_XIVa may increase the incidence of enterovirus infection and is not conducive to the elimination of inflammatory factors in children with HFMD.…”

Section: Discussionmentioning

confidence: 99%

Changes in the intestinal microbiota of children with hand, foot, and mouth disease under 3 years old

et al. 2023

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This study aimed to clarify the characteristics of intestinal microbiota in children with hand, foot, and mouth disease (HFMD) under 3 years old. Fresh feces were collected from 54 children with HFMD and 30 healthy children. All of them were <3 years old. Sequencing of the 16S rDNA amplicons was performed. Between the 2 groups, the richness, diversity, and structure of the intestinal microbiota were analyzed by α-diversity and β-diversity. Linear discriminant analysis and LEfSe analyses were used to compare different bacterial classifications. The sex and age of the children in the 2 groups were not statistically significant (P = .92 and P = .98, respectively). Compared to healthy children, the Shannon index, Ace index, and Chao index were lower in children with HFMD (P = .027, P = .012, and P = .012, respectively). Based on the weighted or unweighted UniFrac distance analysis, the structure of the intestinal microbiota in HFMD was also significantly changed (P = .002 and P < .001, respectively). Linear discriminant analysis and LEfSe analysis showed that the changes of key bacteria were manifested as a decrease in Prevotella and Clostridium_XIVa (P < .001 and P < .001, respectively), while Escherichia and Bifidobacterium increased (P = .025 and P = .001, respectively). Children with HFMD under 3 years of age have intestinal microbiota disorder and show a decrease in diversity and richness. The decrease in the abundance of Prevotella and Clostridium, which can produce short-chain fatty acids, is also one of the characteristics of the change. These results can offer a theoretical foundation for the pathogenesis and microecological treatment of HFMD in infants.

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Section: Discussionmentioning

confidence: 99%

Changes in the intestinal microbiota of children with hand, foot, and mouth disease under 3 years old

et al. 2023

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“…Emerging evidence suggests the role of immunopathogenesis in pulmonary edema. Several studies have shown that CD4+ T cells, CD8+ T cells, and natural killer (NK) cells were depleted in HFMD patients with pulmonary edema 21–23 . Our previous studies found that neutrophils, macrophages, and mast cells contributed to EVA71‐induced pulmonary edema 24,25 .…”

Section: Introductionmentioning

confidence: 97%

“…Several studies have shown that CD4+ T cells, CD8+ T cells, and natural killer (NK) cells were depleted in HFMD patients with pulmonary edema. [21][22][23] Our previous studies found that neutrophils, macrophages, and mast cells contributed to EVA71induced pulmonary edema. 24,25 In addition, the concentrations of inflammatory cytokines and chemokines were increased in severe HFMD patients with pulmonary edema compared with mild patients.…”

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confidence: 97%

Local immune dysregulation and subsequent inflammatory response contribute to pulmonary edema caused by Enterovirus infection in mice

Sun

Liu

Dai

et al. 2023

Journal of Medical Virology

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Pulmonary edema that comes on suddenly is the leading cause of mortality in handfoot-and-mouth disease (HFMD) patients; however, its pathogenesis is still largely unclear. A range of research suggest immunopathogenesis during the occurrence of pulmonary edema in severe HFMD patients. Herein, to investigate the potential mechanism of immune dysregulation in the development of pulmonary edema upon Enterovirus (EV) infection, we established mouse infection models for Enteroviruses (EVs) including Coxsackievirus (CV) A6, Enterovirus A71 (EVA71), and CVA2 exhibiting a high incidence of pulmonary edema. We found that EVs infection induced an immune system disorder by reducing the numbers of pulmonary and circulatory T cells, B cells, macrophages, and monocytes and increasing the numbers of lung neutrophils, myeloid-derived suppressor cells (MDSCs), and activated T cells. In addition, the concentrations of C−X−C motif chemokine ligand 1 (CXCL-1), tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and interleukin 6 were increased in EV-infected lungs. Moreover, we found that EVs replication in mice lungs lead to apoptosis of lung cells and degradation of tight junction proteins. In conclusion, EVs infection likely triggered a complexed immune defense mechanism and caused dysregulation of innate immune cells (MDSCs, neutrophils, monocytes, and macrophages) and adaptive cellular immunity (B cells, T cells). This dysregulation increased the release of cytokines and other inflammatory factors from activated immune-related cells and caused lung barrier damage and pulmonary edema.

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Modulation of plasmacytoid dendritic cell and CD4+ T cell differentiation accompanied by upregulation of the cholinergic anti-inflammatory pathway induced by enterovirus 71

Li,

Huang,

Liu

et al. 2024

Arch Virol

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Low-frequency, exhausted immune status of CD56dim NK cells and disordered inflammatory cytokine secretion of CD56bright NK cells associated with progression of severe HFMD, especially in EV71-infected patients

Cited by 6 publications

References 43 publications

Changes in the intestinal microbiota of children with hand, foot, and mouth disease under 3 years old

Changes in the intestinal microbiota of children with hand, foot, and mouth disease under 3 years old

Local immune dysregulation and subsequent inflammatory response contribute to pulmonary edema caused by Enterovirus infection in mice

Modulation of plasmacytoid dendritic cell and CD4+ T cell differentiation accompanied by upregulation of the cholinergic anti-inflammatory pathway induced by enterovirus 71

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