Immune cell phenotypes associated with disease severity and long-term neutralizing antibody titers after natural dengue virus infection

免疫细胞表型与自然感染登革热病毒后的疾病严重程度和长期中和抗体滴度相关

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作者:Angeline Rouers, Melissa Hui Yen Chng, Bernett Lee, Menaka P Rajapakse, Kaval Kaur, Ying Xiu Toh, Durgalakshmi Sathiakumar, Thomas Loy, Tun-Linn Thein, Vanessa W X Lim, Amit Singhal, Tsin Wen Yeo, Yee-Sin Leo, Kalpit A Vora, Danilo Casimiro, Bing Lim, Lisa Tucker-Kellogg, Laura Rivino, Evan W Newell

Abstract

Prior immunological exposure to dengue virus can be both protective and disease-enhancing during subsequent infections with different dengue virus serotypes. We provide here a systematic, longitudinal analysis of B cell, T cell, and antibody responses in the same patients. Antibody responses as well as T and B cell activation differentiate primary from secondary responses. Hospitalization is associated with lower frequencies of activated, terminally differentiated T cells and higher percentages of effector memory CD4 T cells. Patients with more severe disease tend to have higher percentages of plasmablasts. This does not translate into long-term antibody titers, since neutralizing titers after 6 months correlate with percentages of specific memory B cells, but not with acute plasmablast activation. Overall, our unbiased analysis reveals associations between cellular profiles and disease severity, opening opportunities to study immunopathology in dengue disease and the potential predictive value of these parameters.

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