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Dysregulated TGF-β Production Underlies the Age-Related Vulnerability to Chikungunya Virus
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نویسنده
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uhrlaub j.l. ,pulko v. ,defilippis v.r. ,broeckel r. ,streblow d.n. ,coleman g.d. ,park b.s. ,lindo j.f. ,vickers i. ,anzinger j.j. ,nikolich-žugich j.
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منبع
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plos pathogens - 2016 - دوره : 12 - شماره : 10
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چکیده
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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 tgfβ production during acute infection leads to a reduced immune response and subsequent chronic disease. humans suffering from chikv infection also exhibited high tgfβ levels and a pronounced age-related defect in neutralizing anti-chikv antibody production. in vivo reduction of tgfβ levels minimized acute joint swelling,restored neutralizing antibody production and diminished chronic joint pathology in old mice. this study identifies increased and dysregulated tgfβ secretion as one key mechanism contributing to the age-related loss of protective anti-chikv-immunity leading to chronic chikvd. © 2016 uhrlaub et al.
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آدرس
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department of immunobiology and the arizona center on aging,university of arizona college of medicine,tucson,az, United States, department of immunobiology and the arizona center on aging,university of arizona college of medicine,tucson,az,united states,roche glycart ag,schlieren, Switzerland, vaccine and gene therapy institute,oregon health and science university,beaverton,or, United States, vaccine and gene therapy institute,oregon health and science university,beaverton,or, United States, vaccine and gene therapy institute,oregon health and science university,beaverton,or, United States, charles river,ashland,oh, United States, division of biostatistics,department of public health and preventive medicine,oregon health and science university,portland,or, United States, department of microbiology,university of the west indies,mona,kingston, Jamaica, department of microbiology,university of the west indies,mona,kingston, Jamaica, department of microbiology,university of the west indies,mona,kingston, Jamaica, department of immunobiology and the arizona center on aging,university of arizona college of medicine,tucson,az, United States
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Authors
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