Muscle Tissue Damage and Recovery After EV71 Infection Correspond to Dynamic Macrophage Phenotypes
Enterovirus 71 (EV71) is a positive single-stranded RNA virus from the enterovirus genus of the Picornaviridae family. Most young children infected with EV71 develop mild symptoms of hand, foot and mouth disease, but some develop severe symptoms with neurological involvement. Limb paralysis from EV7...
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.648184/full |
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| author | Mei-Yi Lu Ya-Lin Lin Yali Kuo Chi-Fen Chuang Jen-Ren Wang Jen-Ren Wang Jen-Ren Wang Jen-Ren Wang Fang Liao |
| author_facet | Mei-Yi Lu Ya-Lin Lin Yali Kuo Chi-Fen Chuang Jen-Ren Wang Jen-Ren Wang Jen-Ren Wang Jen-Ren Wang Fang Liao |
| author_sort | Mei-Yi Lu |
| collection | DOAJ |
| description | Enterovirus 71 (EV71) is a positive single-stranded RNA virus from the enterovirus genus of the Picornaviridae family. Most young children infected with EV71 develop mild symptoms of hand, foot and mouth disease, but some develop severe symptoms with neurological involvement. Limb paralysis from EV71 infection is presumed to arise mainly from dysfunction of motor neurons in the spinal cord. However, EV71 also targets and damages skeletal muscle, which may also contribute to the debilitating symptoms. In this study, we have delineated the impacts of EV71 infection on skeletal muscle using a mouse model. Mouse pups infected with EV71 developed limb paralysis, starting at day 3 post-infection and peaking at day 5-7 post-infection. At later times, mice recovered gradually but not completely. Notably, severe disease was associated with high levels of myositis accompanied by muscle calcification and persistent motor end plate abnormalities. Interestingly, macrophages exhibited a dynamic change in phenotype, with inflammatory macrophages (CD45+CD11b+Ly6Chi) appearing in the early stage of infection and anti-inflammatory/restorative macrophages (CD45+CD11b+Ly6Clow/-) appearing in the late stage. The presence of inflammatory macrophages was associated with severe inflammation, while the restorative macrophages were associated with recovery. Altogether, we have demonstrated that EV71 infection causes myositis, muscle calcification and structural defects in motor end plates. Subsequent muscle regeneration is associated with a dynamic change in macrophage phenotype. |
| first_indexed | 2024-12-16T18:51:33Z |
| format | Article |
| id | doaj.art-3296d99ab58e4681b857eefa3d244114 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-16T18:51:33Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3296d99ab58e4681b857eefa3d2441142022-12-21T22:20:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-07-011210.3389/fimmu.2021.648184648184Muscle Tissue Damage and Recovery After EV71 Infection Correspond to Dynamic Macrophage PhenotypesMei-Yi Lu0Ya-Lin Lin1Yali Kuo2Chi-Fen Chuang3Jen-Ren Wang4Jen-Ren Wang5Jen-Ren Wang6Jen-Ren Wang7Fang Liao8Institute of Biomedical Sciences, Academia Sinica, Taipei, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan, TaiwanDepartment of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan, TaiwanDepartment of Pathology, National Cheng Kung University Hospital, Tainan, TaiwanCenter of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei, TaiwanEnterovirus 71 (EV71) is a positive single-stranded RNA virus from the enterovirus genus of the Picornaviridae family. Most young children infected with EV71 develop mild symptoms of hand, foot and mouth disease, but some develop severe symptoms with neurological involvement. Limb paralysis from EV71 infection is presumed to arise mainly from dysfunction of motor neurons in the spinal cord. However, EV71 also targets and damages skeletal muscle, which may also contribute to the debilitating symptoms. In this study, we have delineated the impacts of EV71 infection on skeletal muscle using a mouse model. Mouse pups infected with EV71 developed limb paralysis, starting at day 3 post-infection and peaking at day 5-7 post-infection. At later times, mice recovered gradually but not completely. Notably, severe disease was associated with high levels of myositis accompanied by muscle calcification and persistent motor end plate abnormalities. Interestingly, macrophages exhibited a dynamic change in phenotype, with inflammatory macrophages (CD45+CD11b+Ly6Chi) appearing in the early stage of infection and anti-inflammatory/restorative macrophages (CD45+CD11b+Ly6Clow/-) appearing in the late stage. The presence of inflammatory macrophages was associated with severe inflammation, while the restorative macrophages were associated with recovery. Altogether, we have demonstrated that EV71 infection causes myositis, muscle calcification and structural defects in motor end plates. Subsequent muscle regeneration is associated with a dynamic change in macrophage phenotype.https://www.frontiersin.org/articles/10.3389/fimmu.2021.648184/fullEV71enterovirusmyositisskeletal musclecalcificationmacrophages |
| spellingShingle | Mei-Yi Lu Ya-Lin Lin Yali Kuo Chi-Fen Chuang Jen-Ren Wang Jen-Ren Wang Jen-Ren Wang Jen-Ren Wang Fang Liao Muscle Tissue Damage and Recovery After EV71 Infection Correspond to Dynamic Macrophage Phenotypes Frontiers in Immunology EV71 enterovirus myositis skeletal muscle calcification macrophages |
| title | Muscle Tissue Damage and Recovery After EV71 Infection Correspond to Dynamic Macrophage Phenotypes |
| title_full | Muscle Tissue Damage and Recovery After EV71 Infection Correspond to Dynamic Macrophage Phenotypes |
| title_fullStr | Muscle Tissue Damage and Recovery After EV71 Infection Correspond to Dynamic Macrophage Phenotypes |
| title_full_unstemmed | Muscle Tissue Damage and Recovery After EV71 Infection Correspond to Dynamic Macrophage Phenotypes |
| title_short | Muscle Tissue Damage and Recovery After EV71 Infection Correspond to Dynamic Macrophage Phenotypes |
| title_sort | muscle tissue damage and recovery after ev71 infection correspond to dynamic macrophage phenotypes |
| topic | EV71 enterovirus myositis skeletal muscle calcification macrophages |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.648184/full |
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