Dysregulated TGF-β Production Underlies the Age-Related Vulnerability to Chikungunya Virus
AuthorUhrlaub, Jennifer L.
DeFilippis, Victor R.
Streblow, Daniel N.
Coleman, Gary D.
Park, Byung S.
Lindo, John F.
Anzinger, Joshua J.
AffiliationUniv Arizona, Coll Med, Dept Immunobiol
Univ Arizona, Coll Med, Arizona Ctr Aging
MetadataShow full item record
PublisherPUBLIC LIBRARY SCIENCE
CitationDysregulated TGF-β Production Underlies the Age-Related Vulnerability to Chikungunya Virus 2016, 12 (10):e1005891 PLOS Pathogens
Rights© 2016 Uhrlaub et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.
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AbstractChikungunya 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 TGF beta production during acute infection leads to a reduced immune response and subsequent chronic disease. Humans suffering from CHIKV infection also exhibited high TGF beta levels and a pronounced age-related defect in neutralizing anti-CHIKV antibody production. In vivo reduction of TGF beta levels minimized acute joint swelling, restored neutralizing antibody production and diminished chronic joint pathology in old mice. This study identifies increased and dysregulated TGF beta secretion as one key mechanism contributing to the age-related loss of protective anti-CHIKV-immunity leading to chronic CHIKVD.
NoteOpen Access Journal.
VersionFinal published version
SponsorsNIH [U54 AI081680]