Dysregulated TGF-ß Production Underlies the Age-Related Vulnerability to Chikungunya Virus.
PLoS Pathog
; 12(10): e1005891, 2016 Oct.
Article
en En
| MEDLINE
| ID: mdl-27736984
ABSTRACT
Chikungunya virus (CHIKV) is a re-emerging global pathogen with pandemic potential, which causes fever, rash and debilitating arthralgia. Older adults over 65 years are particularly susceptible to severe and chronic CHIKV disease (CHIKVD), accounting for >90% of all CHIKV-related deaths. There are currently no approved vaccines or antiviral treatments available to limit chronic CHIKVD. Here we show that in old mice excessive, dysregulated TGFß production during acute infection leads to a reduced immune response and subsequent chronic disease. Humans suffering from CHIKV infection also exhibited high TGFß levels and a pronounced age-related defect in neutralizing anti-CHIKV antibody production. In vivo reduction of TGFß levels minimized acute joint swelling, restored neutralizing antibody production and diminished chronic joint pathology in old mice. This study identifies increased and dysregulated TGFß secretion as one key mechanism contributing to the age-related loss of protective anti-CHIKV-immunity leading to chronic CHIKVD.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Envejecimiento
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Factor de Crecimiento Transformador beta
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Fiebre Chikungunya
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Aged
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Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
PLoS Pathog
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos