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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Microbiol. | doi: 10.3389/fmicb.2019.02225

Macrophage Migration Inhibitory Factor Triggers Inflammatory Responses during Very Virulent Infectious Bursal Disease Virus Infection

 Aijing Liu1, Hui Li1,  Xiaole Qi1,  Qi Wang1, Bo Yang1, Tiantian Wu1, Nana Yan1, Yue Li1,  Qing Pan1,  Yulong Gao1, Li Gao1, Changjun Liu1, Yanping Zhang1,  Hongyu Cui1,  Kai Li1, Yongqiang Wang1* and  Xiaomei Wang1*
  • 1Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, China

Infectious bursal disease (IBD) is one of the main threats to the poultry industry worldwide. In China, very virulent IBD virus (vvIBDV) is the main prevalent virus strain, causing inflammation, immunosuppression, and high mortality in young chickens. To determine whether this acute inflammation can trigger lesions or even death in chickens, it is important to study the mechanism of vvIBDV pathogenicity. Thus, in the current study, we investigated the inflammation response, bursal lesions, and mortality in chickens caused by vvIBDV at different time points post the infection. Results showed an upregulation of proinflammatory cytokines, including interleukin-1β and interleukin-18, and macrophage infiltration in bursa in response to vvIBDV infection. High-throughput proteomic sequencing based on isobaric tags for relative and absolute quantitation showed that chicken macrophage migration inhibitory factor (chMIF) was upregulated uniquely in primary B cells infected with vvIBDV, compared with infection by non-pathogenic attenuated IBDV. We confirmed that chMIF was upregulated by vvIBDV infection both in vivo and in vitro. Moreover, chMIF was extracellularly secreted by infected DT40 and primary B cells. Further experiments revealed that the secreted chMIF could induce migration of peripheral blood mononuclear cells and promote transcription of proinflammatory cytokines in chicken primary macrophages. Notably, these effects of chMIF could be reduced by using an MIF specific inhibitor. Thus, our study elucidates critical molecular determinants underlying vvIBDV-mediated initiation of acute inflammation, which might be pivotal to understand the mechanism of vvIBDV pathogenicity.

Keywords: vvIBDV, Inflammation, MIF, macrophage, proinflammatory cytokines

Received: 13 Jul 2019; Accepted: 11 Sep 2019.

Copyright: © 2019 Liu, Li, Qi, Wang, Yang, Wu, Yan, Li, Pan, Gao, Gao, Liu, Zhang, Cui, Li, Wang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Yongqiang Wang, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China, wangyongqiang@caas.cn
Prof. Xiaomei Wang, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China, wangxiaomei@caas.cn