Tregs control the development of symptomatic West Nile virus infection in humans and mice. Export

@article{citeulike:6079709, 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.}, author = {Lanteri, Marion C. and O'Brien, Katie M. and Purtha, Whitney E. and Cameron, Mark J. and Lund, Jennifer M. and Owen, Rachel E. and Heitman, John W. and Custer, Brian and Hirschkorn, Dale F. and Tobler, Leslie H. and Kiely, Nancy and Prince, Harry E. and Ndhlovu, Lishomwa C. and Nixon, Douglas F. and Kamel, Hany T. and Kelvin, David J. and Busch, Michael P. and Rudensky, Alexander Y. and Diamond, Michael S. and Norris, Philip J.}, citeulike-article-id = {6079709}, citeulike-linkout-0 = {http://dx.doi.org/10.1172/JCI39387}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19855131}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19855131}, doi = {10.1172/JCI39387}, issn = {1558-8238}, journal = {The Journal of clinical investigation}, keywords = {treg, treg\_infection}, month = {November}, number = {11}, pages = {3266--3277}, posted-at = {2009-11-06 00:33:57}, priority = {4}, title = {Tregs control the development of symptomatic West Nile virus infection in humans and mice.}, url = {http://dx.doi.org/10.1172/JCI39387}, volume = {119}, year = {2009} }

TY - JOUR ID - citeulike:6079709 L3 - citeulike-article-id:6079709 N2 - 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. IS - 11 JF - The Journal of clinical investigation SN - 1558-8238 EP - 3277 TI - Tregs control the development of symptomatic West Nile virus infection in humans and mice. VL - 119 SP - 3266 KW - treg KW - treg_infection AU - Lanteri, Marion AU - O'Brien, Katie AU - Purtha, Whitney AU - Cameron, Mark AU - Lund, Jennifer AU - Owen, Rachel AU - Heitman, John AU - Custer, Brian AU - Hirschkorn, Dale AU - Tobler, Leslie AU - Kiely, Nancy AU - Prince, Harry AU - Ndhlovu, Lishomwa AU - Nixon, Douglas AU - Kamel, Hany AU - Kelvin, David AU - Busch, Michael AU - Rudensky, Alexander AU - Diamond, Michael AU - Norris, Philip PY - 2009/11// UR - http://dx.doi.org/10.1172/JCI39387 ER -