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Tregs control the development of symptomatic West Nile virus infection in humans and mice.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2009 Nov; Vol. 119 (11), pp. 3266-77. Date of Electronic Publication: 2009 Oct 12. - Publication Year :
- 2009
-
Abstract
- West Nile virus (WNV) causes asymptomatic infection in most humans, but for undefined reasons, approximately 20% of immunocompetent individuals develop West Nile fever, a potentially debilitating febrile illness, and approximately 1% develop neuroinvasive disease syndromes. Notably, since its emergence in 1999, WNV has become the leading cause of epidemic viral encephalitis in North America. We hypothesized that CD4+ Tregs might be differentially regulated in subjects with symptomatic compared with those with asymptomatic WNV infection. Here, we show that in 32 blood donors with acute WNV infection, Tregs expanded significantly in the 3 months after index (RNA+) donations in all subjects. Symptomatic donors exhibited lower Treg frequencies from 2 weeks through 1 year after index donation yet did not show differences in systemic T cell or generalized inflammatory responses. In parallel prospective experimental studies, symptomatic WNV-infected mice also developed lower Treg frequencies compared with asymptomatic mice at 2 weeks after infection. Moreover, Treg-deficient mice developed lethal WNV infection at a higher rate than controls. Together, these results suggest that higher levels of peripheral Tregs after infection protect against severe WNV disease in immunocompetent animals and humans.
- Subjects :
- Adult
Aged
Animals
Blood Donors
Cell Proliferation
Female
Humans
Immunity, Innate
Lymphocyte Count
Male
Mice
Mice, Inbred C57BL
Middle Aged
Phenotype
RNA, Viral blood
Time Factors
West Nile Fever mortality
West Nile Fever physiopathology
West Nile virus physiology
Young Adult
T-Lymphocytes, Regulatory cytology
T-Lymphocytes, Regulatory immunology
West Nile Fever immunology
West Nile Fever pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1558-8238
- Volume :
- 119
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 19855131
- Full Text :
- https://doi.org/10.1172/JCI39387