Muscle Tissue Damage and Recovery After EV71 Infection Correspond to Dynamic Macrophage Phenotypes

Frontiers in Immunology, 2021 · DOI: 10.3389/fimmu.2021.648184 · Published: July 9, 2021

Simple Explanation

Enterovirus 71 (EV71) primarily affects young children, causing hand, foot, and mouth disease, and can lead to severe neurological complications including limb paralysis. This study investigates the impact of EV71 on skeletal muscles in a mouse model. The research found that EV71 infection in mice causes severe myositis, muscle calcification, and structural defects in motor end plates. The damage and subsequent muscle regeneration were associated with dynamic changes in macrophage phenotypes. The study highlights the role of different macrophage types: inflammatory macrophages appearing early in the infection, and anti-inflammatory/restorative macrophages appearing later during recovery, suggesting their importance in muscle repair and regeneration.

Study Duration

Not specified

Participants

Mouse pups (11-12 days old)

Evidence Level

Not specified

Key Findings

1
EV71 infection induces severe myositis and muscle calcification in mice, contributing to limb paralysis. The muscle damage peaks at 5-7 days post-infection, followed by gradual recovery.
2
The study identifies a dynamic change in macrophage phenotypes during EV71 infection. Inflammatory macrophages (Ly6Chi) dominate early, while anti-inflammatory/restorative macrophages (Ly6Clow/-) increase during the recovery phase.
3
EV71 infection impairs the postsynaptic structure of neuromuscular junctions (NMJs). Motor end plates show structural damage that is not fully repaired even months after infection.

Research Summary

This study demonstrates that EV71 infection in mice leads to significant muscle tissue damage, including myositis and calcification, which contributes to limb paralysis. The research highlights the importance of considering muscle damage, in addition to CNS effects, in EV71-induced paralysis. The study elucidates the dynamic roles of different macrophage phenotypes in the progression and resolution of EV71-induced myositis. Inflammatory macrophages contribute to early inflammation and viral clearance, while anti-inflammatory macrophages promote tissue repair and muscle regeneration. EV71 infection also causes persistent structural defects in neuromuscular junctions, which may further impair muscle function. This finding suggests that therapeutic strategies should target both muscle regeneration and NMJ repair to improve outcomes in EV71-infected patients.

Practical Implications

Therapeutic Strategies

Targeting both muscle regeneration and neuromuscular junction repair may improve outcomes in EV71-infected patients.

Macrophage Modulation

Modulating macrophage phenotypes could be a potential therapeutic approach to enhance muscle repair and reduce inflammation in EV71 infections.

Understanding Pathogenesis

A better understanding of EV71's impact on muscle tissue can lead to more comprehensive treatment strategies for limb paralysis.

Study Limitations

1
The study uses a mouse model, which may not fully replicate the human response to EV71 infection.
2
The mechanisms regulating the interchangeable macrophage phenotypes during EV71 infection remain to be fully investigated.
3
The long-term functional consequences of the observed NMJ structural defects were not thoroughly examined.

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