A balanced game: chicken macrophage response to ALV-J infection
A balanced game: chicken macrophage response to ALV-J infection
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平衡游戏：鸡巨噬细胞对 ALV-J 感染的反应
DOI：
10.1186/s13567-019-0638-y
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发表时间：
2019-03-06
影响因子：
4.4
通讯作者：
Zhang, Xiquan
中科院分区：
文献类型：
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作者：
Feng, Min;Xie, Tingting;Zhang, Xiquan
J亚群禽白血病病毒（ALV-J）感染可引起雏鸡肿瘤和免疫抑制。巨噬细胞在宿主防御入侵病原体中起着核心作用。在本研究中，我们发现了一个有趣的现象：ALV-J的复制从感染后3小时（hpi）减弱到36 hpi，这是用Western blotting和RT-PCR验证。为了进一步研究ALV-J与巨噬细胞之间的相互作用，本研究采用转录组学方法分析了宿主基因在鸡原代单核细胞源性巨噬细胞（MDM）中的功能。与未感染对照组相比，在感染后3 h，在鸡MDM中分别鉴定出624个上调的差异表达基因（DEG）和341个下调的DEG，在感染后36 h，分别鉴定出174个上调的DEG和87个下调的DEG。基因本体和KEGG通路分析结果表明，ALV-J感染后3 hpi诱导了鸡MDM的天然免疫应答，而不是36 hpi。在ALV-J感染过程中，MIP-3α、IL-1β、iNOS、K60、IRG 1、CH 25 H、NFKBIZ、溶菌酶和OASL等宿主因子的表达上调参与了宿主的防御反应。相反，上调EX-FABP、IL 4 I 1、考克斯-2、NF κ BIA、TNFAIP 3和Jak STAT通路抑制剂CISH、SOCS 1和SOCS 3则有利于ALV-J在鸡巨噬细胞中的存活。我们推测ALV-J对巨噬细胞的嗜性有助于在鸡MDM中从6至36 hpi建立潜伏感染。本研究对鸡巨噬细胞与ALV-J的相互作用进行了全面的研究，揭示了鸡巨噬细胞防御ALV-J入侵的机制以及ALV-J如何逃避宿主的天然免疫应答。
Avian leukosis virus subgroup J (ALV-J) infection can cause tumors and immunosuppression in infected chickens. Macrophages play a central role in host defense against invading pathogens. In this study, we discovered an interesting phenomenon: ALV-J replication is weakened from 3 hours post-infection (hpi) to 36 hpi, which was verified using Western blotting and RT-PCR. To further investigate the interaction between ALV-J and macrophages, transcriptome analysis was performed to analyze the host genes’ function in chicken primary monocyte-derived macrophages (MDM). Compared to the uninfected control, 624 up-regulated differentially expressed genes (DEG) and 341 down-regulated DEG at 3 hpi, and 174 up-regulated DEG and 87 down-regulated DEG at 36 hpi were identified in chicken MDM, respectively. ALV-J infection induced strong innate immune responses in chicken MDM at 3 hpi, instead of 36 hpi, according to the analysis results of Gene Ontology and KEGG pathway. Importantly, the host factors, such as up-regulatedMIP-3α,IL-1β,iNOS,K60,IRG1,CH25H,NFKBIZ, lysozyme andOASLwere involved in the host defense response during the course of ALV-J infection. On the contrary, up-regulatedEX-FABP,IL4I1,COX-2,NFKBIA,TNFAIP3and the Jak STAT pathway inhibitors includingCISH,SOCS1andSOCS3are beneficial to ALV-J survival in chicken macrophages. We speculated that ALV-J tropism for macrophages helps to establish a latent infection in chicken MDM from 6 to 36 hpi. The present study provides a comprehensive view of the interactions between macrophages and ALV-J. It suggests the mechanisms of defense of chicken macrophages against ALV-J invasion and how ALV-J escape the host innate immune responses.