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Front. Immunol. | doi: 10.3389/fimmu.2018.00366

Enhanced replication of virulent Newcastle disease virus in chicken macrophages is due to polarized activation of cells by inhibition of TLR7

 Pingze Zhang1, Zhuang Ding1*, Xinxin Liu2, Yanyu Cheng1, Zhi Tao1, Lili Ai1, Cong Xue1, Jing Qian1, Xueli Wang3, Yuhai Bi4, Tobias Stoeger5 and  Renfu Yin1*
  • 1Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Jilin University, China
  • 2College of Food Science and Engineering, Jilin University, China
  • 3College of Animal Science and Technology, Inner Mongolia University for Nationalities, China
  • 4CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, China
  • 5Comprehensive Pneumology Center, Institute of Lung Biology and Disease (iLBD), Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt, Germany

Newcastle disease (ND), caused by infections with virulent strains of Newcastle disease virus (NDV), is one of the most important infectious disease affecting wild, peridomestic, and domestic birds worldwide. Vaccines constructed from live, low-virulence (lentogenic) viruses are the most accepted prevention and control strategies for combating ND in poultry across the globe. Avian macrophages are one of the first cell lines of defense against microbial infection, responding to signals in the microenvironment. Although macrophages are considered to be one of the main target cells for NDV infection in vivo, very little is known about the ability of NDV to infect chicken macrophages, and virulence mechanisms of NDV as well as the polarized activation patterns of macrophages and correlation with viral infection and replication. In the present study, a cell culture model (chicken bone marrow macrophage cell line HD11) and three different virulence and genotypes of NDV (including class II virulent NA-1, class II lentogenic LaSota and class I lentogenic F55) were used to solve the above underlying questions. Our data indicated that all three NDV strains had similar replication rates during the early stages of infection. Virulent NDV titers was shown to increase compared to the other lentogenic strains, and this growth was associated with a strong up-regulation of both pro-inflammatory M1-like markers/cytokines and anti-inflammatory M2-like markers/cytokines in chicken macrophages. Virulent NDV was found to block Toll-like receptor (TLR) 7 expression, inducing higher expression of type I interferons in chicken macrophages at the late stage of viral infection. Only virulent NDV replication can be inhibited by pretreatment with TLR7 ligand. Overall, this study demonstrated that virulent NDV activates a M1-/M2-like mixed polarized activation of chicken macrophages by inhibition of TLR7, resulting in enhanced replication compared to lentogenic viruses.

Keywords: Chicken macrophages, Newcastle disease virus, Toll-like receptor (TLR) 7, Macrophage polarized activation, Virus growth, immune response

Received: 15 Aug 2017; Accepted: 09 Feb 2018.

Edited by:

Geanncarlo Lugo-Villarino, UMR5089 Institut de Pharmacologie et de Biologie Structurale (IPBS), France

Reviewed by:

Mohammad Heidari, Agricultural Research Service (USDA), United States
Mohamed Faizal Abdul-Careem, University of Calgary, Canada
Christine Jansen, Utrecht University, Netherlands  

Copyright: © 2018 Zhang, Ding, Liu, Cheng, Tao, Ai, Xue, Qian, Wang, Bi, Stoeger and Yin. 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 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:
Prof. Zhuang Ding, Jilin University, Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Changchun, China, dingzhuang@jlu.edu.cn
Dr. Renfu Yin, Jilin University, Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Changchun, China, yin@jlu.edu.cn