ZIKV infection induces robust Th1-like Tfh cell and long-term protective antibody responses in immunocompetent mice

• Published in: Nature communications Vol. 10; no. 1; pp. 3859 - 16
• Main Authors: Liang, Huabin, Tang, Jinyi, Liu, Zhihua, Liu, Yuanhua, Huang, Yuanyuan, Xu, Yongfen, Hao, Pei, Yin, Zhinan, Zhong, Jin, Ye, Lilin, Jin, Xia, Wang, Haikun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.08.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 38/1; 38/91; 631/250/2152/1566/2493; 631/250/2152/2153/1982; 631/250/590; 631/326/596/2553; 64/60; Animals; Antibodies; Antibodies, Neutralizing - immunology; Antibodies, Neutralizing - metabolism; Antibodies, Viral - immunology; Antibodies, Viral - metabolism; Antibody response; Antigens; Chlorocebus aethiops; Class switching; Gene expression; Host Microbial Interactions - immunology; Humanities and Social Sciences; Immunization; Immunocompetence; Immunoglobulin Class Switching - immunology; Immunoglobulin G - genetics; Immunoglobulin G - immunology; Infections; Interferon-gamma - genetics; Interferon-gamma - immunology; Interferon-gamma - metabolism; Lymphocytes T; Mice; Mice, Knockout; multidisciplinary; Science; Science (multidisciplinary); Signal Transduction - immunology; Surface markers; T-Box Domain Proteins - metabolism; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; Vaccination; Vector-borne diseases; Vero Cells; Viruses; Zika Virus - immunology; Zika Virus Infection - immunology; Zika Virus Infection - virology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-11754-0

Induction of long-lived antibody responses during infection or vaccination is often essential for subsequent protection, but the relative contributions of T follicular helper (Tfh) cells and T helper 1 (Th1) cells for induction of antigen specific antibody responses to viruses are unclear. Here, we establish an acute Zika virus (ZIKV) infection model in immunocompetent mice, and show that ZIKV infection elicits robust Th1-like Tfh cell and protective antibody responses. While these Th1-like Tfh cells share phenotypic and transcriptomic profiles with both Tfh and Th1 cells, they also have unique surface markers and gene expression characteristics, and are dependent on T-bet for their development. Th1-like Tfh cells, but not Th1 cells, are essential for class switching of ZIKV-specific IgG2c antibodies and maintenance of long-term neutralizing antibody responses. Our study suggests that specific modulation of the Th1-like Tfh cell response during infection or vaccination may augment the induction of antiviral antibody response to ZIKV and other viruses. Here, the authors show that Zika virus (ZIKV) infection induces Th1-like Tfh cells that depend on T-bet for their development and are essential for class switching of ZIKV-specific IgG2c antibodies and maintenance of long-term neutralizing antibody responses.