Enterovirus 71 Infection of Human Dendritic Cells

Lin, Yu Wen; Wang, Shainn Wei; Tung, Yuk Ying; Chen, Shun Hua

doi:10.3181/0903-rm-116

Cited by 68 publications

(73 citation statements)

References 34 publications

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“…Survival rates and clinical scores indicated that the treated animals died significantly faster than the untreated infected mice (Fig. 8), thus supporting previous observations with IL-6 KO mice (26). Consistently, mice cotreated with anti-IL-6 antibodies at the time of infection displayed severe tissue (limb muscle) damage, with myonecrosis even more pronounced than in the untreated infected animals, and spleen atrophy (Fig.…”

Section: Vol 85 2011 Role Of Il-6 During Ev71 Infection 3071supporting

confidence: 77%

“…Previous literature reported that IL-6 knockout (KO) mice were more susceptible to EV71 infection than their parental counterparts, suggesting a protective role for IL-6 during EV71 infection (26). In contrast, we found that anti-IL-6 antibody treatment resulted in better survival and clinical outcome, thus suggesting instead that IL-6 is detrimental to the host.…”

Section: Vol 85 2011 Role Of Il-6 During Ev71 Infection 3071contrasting

confidence: 55%

“…10A), in contrast to a previous study that reported higher viral loads in IL-6 KO mice (26). Furthermore, systemic levels of IL-6 in the anti-IL-6-treated animals were higher than the levels measured in the untreated mice (Fig.…”

Section: Vol 85 2011 Role Of Il-6 During Ev71 Infection 3071contrasting

confidence: 54%

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Sustained High Levels of Interleukin-6 Contribute to the Pathogenesis of Enterovirus 71 in a Neonate Mouse Model

Khong

Foo

Trasti

et al. 2011

J Virol

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Enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease (HFMD) in young children and has been consistently associated with the most severe complications of the disease, including central nervous system inflammation and pulmonary edema. Increasing frequency and amplitude of EV71 outbreaks have raised awareness and concerns worldwide. Previous reports proposed that overwhelming virus replication combined with the induction of massive proinflammatory cytokines is responsible for the pathogenicity of EV71. Specifically, elevated interleukin-6 (IL-6) levels were observed consistently in patients and strongly correlated with disease severity. In this study, we show in the neonate mouse model that sustained high levels of IL-6 produced upon EV71 infection lead to severe tissue damage and eventually death of the animals. Administration of anti-IL-6 neutralizing antibodies after the onset of the clinical symptoms successfully improved the survival rates and clinical scores of the infected hosts. Compared to untreated infected controls, anti-IL-6-treated mice displayed reduced tissue damage, absence of splenic atrophy, and increased immune cell activation. In addition, markedly elevated systemic levels of IL-10 were measured in the protected animals. Furthermore, there was no significant difference in virus titers between anti-IL-6-treated mice and untreated mice, indicating that the anti-IL-6 antibody-mediated protection is independent of the virus load. Our findings thus demonstrate that IL-6 plays a major role in EV71-induced immunopathogenesis. As there is still neither vaccine nor treatment available against EV71, anti-IL-6 antibody treatment represents a potential therapeutic approach to providing protection from the most severe complications of the disease.

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Section: Vol 85 2011 Role Of Il-6 During Ev71 Infection 3071supporting

confidence: 77%

Section: Vol 85 2011 Role Of Il-6 During Ev71 Infection 3071contrasting

confidence: 55%

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Sustained High Levels of Interleukin-6 Contribute to the Pathogenesis of Enterovirus 71 in a Neonate Mouse Model

Khong

Foo

Trasti

et al. 2011

J Virol

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“…The cellular and humoral immune responses, such as represented by T cells and the interleukin-6 (IL-6) driven response, are both essential for decreasing the viral load and mortality in EV71-infected mice. 12,13 In humans, an extensive peripheral and central nervous system inflammatory response, with abnormal IL-10, IL-13 and interferon-c (IFN-c) cytokine production as well as lymphocyte depletion, appears to be responsible for the pathogenesis of EV71-associated pulmonary oedema. [14][15][16] However, to date the mechanism of the cellular immune response to EV71 has not been elucidated in detail.…”

Section: M M U N O L O G Y O R I G I N a L A R T I C L Ementioning

confidence: 99%

“…Blood samples were obtained on days 1-7 after onset, discharge from the hospital (day [7][8][9][10][11][12][13][14] and the fully recovered stage (defined as 1 month after illness onset), respectively. All samples were collected specifically for this study and were coded to protect confidentiality.…”

Section: Recruitment and Sample Collectionmentioning

confidence: 99%

Dominant CD4‐dependent RNA‐dependent RNA polymerase‐specific T‐cell responses in children acutely infected with human enterovirus 71 and healthy adult controls

Dang

Gao

et al. 2014

Immunology

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SummaryHuman enterovirus 71 (EV71) is one of the major causes of hand, foot and mouth disease (HFMD), which leads to significant mortality in infected children. A prophylactic vaccine is urgently needed. However, little is known about the protective T-cell immunity in individuals infected with the EV71 virus. In this study, we performed a comprehensive ex vivo interferon-c ELISPOT analysis in 31 children infected with EV71 as well as in 40 healthy adult controls of the CD4 + and CD8 + T-cell responses to overlapping peptides spanning the VP1 structural protein and RNAdependent RNA polymerase (RdRp) non-structural protein. EV71-specific CD4 T-cell responses were detected in most of the acute patients and were mostly CD4-dependent RdRp-specific responses. CD8-dependent VP1 and RdRp-specific responses were also detected in a small proportion of recently infected children. There was no significant association between the strength of the T-cell responses and disease severity observed during the acute EV71 infection phase. Interestingly, an RdRp-specific, but no VP1-specific, CD4-dependent T-cell response was detected in 30% of the adult controls, and no T-cell responses were detected in healthy children. In addition, 24 individual peptides containing potential T-cell epitope regions were identified. The data suggest that CD4-dependent RdRp-specific T-cell responses may play an important role in protective immunity, and the epitopes identified in this study should provide valuable information for future therapeutic and prophylactic vaccine design as well as basic research.

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Role of enterovirus infections in IgE sensitization

Seiskari¹,

Kondrashova²,

Tauriainen³

et al. 2011

Journal of Medical Virology

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Among other infectious agents, enteroviruses have been associated with protection against allergic diseases. The aim of the present study was to confirm these findings using a highly sensitive and specific neutralization antibody assay and to investigate whether the protective effect is related to certain enterovirus serotypes. Antibodies against 12 enterovirus serotypes were measured in 60 children who were positive for allergen-specific IgE and in 190 control children. Echoviruses seemed to be more protective than coxsackie-B-viruses and echovirus 11 had the strongest independent protective effect (P = 0.001; OR = 0.35, 95% CI: 0.18-0.67). The results support previous observations suggesting that infections by certain enterovirus types are associated with protection against IgE sensitization.

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Enterovirus 71 Infection of Human Dendritic Cells

Cited by 68 publications

References 34 publications

Sustained High Levels of Interleukin-6 Contribute to the Pathogenesis of Enterovirus 71 in a Neonate Mouse Model

Sustained High Levels of Interleukin-6 Contribute to the Pathogenesis of Enterovirus 71 in a Neonate Mouse Model

Dominant CD4‐dependent RNA‐dependent RNA polymerase‐specific T‐cell responses in children acutely infected with human enterovirus 71 and healthy adult controls

Role of enterovirus infections in IgE sensitization

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