Dynamics of cellular immune responses in the acute phase of dengue virus infection
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ORIGINAL ARTICLE
Dynamics of cellular immune responses in the acute phase of dengue virus infection Tomoyuki Yoshida • Tsutomu Omatsu • Akatsuki Saito • Yuko Katakai • Yuki Iwasaki • Terue Kurosawa • Masataka Hamano • Atsunori Higashino • Shinichiro Nakamura • Tomohiko Takasaki • Yasuhiro Yasutomi Ichiro Kurane • Hirofumi Akari
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Received: 13 June 2012 / Accepted: 12 December 2012 / Published online: 5 February 2013 Ó Springer-Verlag Wien 2013
Abstract In this study, we examined the dynamics of cellular immune responses in the acute phase of dengue virus (DENV) infection in a marmoset model. Here, we found that DENV infection in marmosets greatly induced responses of CD4/CD8 central memory T and NKT cells. Interestingly, the strength of the immune response was greater in animals infected with a dengue fever strain than in those infected with a dengue hemorrhagic fever strain of DENV. In contrast, when animals were re-challenged with the same DENV strain used for primary infection, the neutralizing antibody induced appeared to play a critical role in sterilizing inhibition against viral replication, resulting in strong but delayed responses of CD4/CD8 central memory T and NKT cells. The results in this study may help to better understand the dynamics of cellular and humoral immune responses in the control of DENV infection.
T. Yoshida and T. Omatsu contributed equally to this study.
Electronic supplementary material The online version of this article (doi:10.1007/s00705-013-1618-6) contains supplementary material, which is available to authorized users. T. Yoshida Y. Iwasaki T. Kurosawa M. Hamano Y. Yasutomi H. Akari Tsukuba Primate Research Center, National Institute of Biomedical Innovation, 1-1 Hachimandai, Tsukuba, Ibaraki 305-0843, Japan T. Yoshida (&) A. Saito A. Higashino H. Akari (&) Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, Inuyama, Aichi 484-8506, Japan e-mail: [email protected] H. Akari e-mail: [email protected]
Introduction Dengue virus (DENV) causes the most prevalent arthropod-borne viral infections in the world [29]. Infection with one of the four serotypes of DENV can lead to dengue fever (DF) and sometimes to fatal dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) [12]. The serious diseases are more likely to develop after secondary infection with a serotype of DENV that is different from that of the primary infection. Infection with DENV induces a high-titered neutralizing antibody response that can provide long-term immunity to the homologous DENV serotype, while the effect of the antibody on the heterologous serotypes is transient [22]. On the other hand, enhanced pathogenicity after secondary DENV infection appears to be explained by antibody-dependent enhancement (ADE). Mouse and monkey experiments have shown that subneutralizing levels of DENV-specific antibodies actually enhance infection [1, 6, 11]. Thus, the development of an effective tetravalent dengue vaccine is considered to
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