TY - JOUR
T1 - Phenotyping of peripheral blood mononuclear cells during acute dengue illness demonstrates infection and increased activation of monocytes in severe cases compared to classic dengue fever
AU - Durbin, Anna P.
AU - Vargas, Maria José
AU - Wanionek, Kimberli
AU - Hammond, Samantha N.
AU - Gordon, Aubree
AU - Rocha, Crisanta
AU - Balmaseda, Angel
AU - Harris, Eva
N1 - Funding Information:
This work was supported by grant AI065359 (NIAID/NIH) and the Broad Institute Microbial Sequencing Center (NIAID/NIH).
PY - 2008/7/5
Y1 - 2008/7/5
N2 - In vitro studies have attempted to identify dengue virus (DEN) target cells in peripheral blood; however, extensive phenotyping of peripheral blood mononuclear cells (PBMCs) from dengue patients has not been reported. PBMCs collected from hospitalized children suspected of acute dengue were analyzed for DEN prM, CD32, CD86, CD14, CD11c, CD16, CD209, CCR7, CD4, and CD8 by flow cytometry to detect DEN antigen in PBMCs and to phenotype DEN-positive cells. DEN prM was detected primarily in activated monocytes (CD14+, CD32+, CD86+, CD11c+). A subset of samples analyzed for DEN nonstructural protein 3 (NS3) confirmed that approximately half of DEN antigen-positive cells contained replicating virus. A higher percentage of PBMCs from DHF patients expressed prM, CD86, CD32, and CD11c than did those from DF patients. Increased activation of monocytes and greater numbers of DEN-infected cells were associated with more severe dengue, implicating a role for monocyte activation in dengue immunopathogenesis.
AB - In vitro studies have attempted to identify dengue virus (DEN) target cells in peripheral blood; however, extensive phenotyping of peripheral blood mononuclear cells (PBMCs) from dengue patients has not been reported. PBMCs collected from hospitalized children suspected of acute dengue were analyzed for DEN prM, CD32, CD86, CD14, CD11c, CD16, CD209, CCR7, CD4, and CD8 by flow cytometry to detect DEN antigen in PBMCs and to phenotype DEN-positive cells. DEN prM was detected primarily in activated monocytes (CD14+, CD32+, CD86+, CD11c+). A subset of samples analyzed for DEN nonstructural protein 3 (NS3) confirmed that approximately half of DEN antigen-positive cells contained replicating virus. A higher percentage of PBMCs from DHF patients expressed prM, CD86, CD32, and CD11c than did those from DF patients. Increased activation of monocytes and greater numbers of DEN-infected cells were associated with more severe dengue, implicating a role for monocyte activation in dengue immunopathogenesis.
KW - Activated monocytes
KW - Dengue
KW - Immunopathogenesis
KW - Infection
KW - Nicaragua
KW - PBMCs
KW - Replication
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U2 - 10.1016/j.virol.2008.03.028
DO - 10.1016/j.virol.2008.03.028
M3 - Article
C2 - 18452966
AN - SCOPUS:44649085672
SN - 0042-6822
VL - 376
SP - 429
EP - 435
JO - Virology
JF - Virology
IS - 2
ER -