Research Papers: Immunology:

Porcine circovirus type 2 activates PI3K/Akt and p38 MAPK pathways to promote interleukin-10 production in macrophages via Cap interaction of gC1qR

Qian Du, Yong Huang, Tongtong Wang, Xiujuan Zhang, Yu Chen, Beibei Cui, Delong Li, Xiaomin Zhao, Wenlong Zhang, Lingling Chang and Dewen Tong _

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Oncotarget. 2016; 7:17492-17507. https://doi.org/10.18632/oncotarget.7362

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Qian Du1,*, Yong Huang1,*, Tongtong Wang1, Xiujuan Zhang1, Yu Chen1, Beibei Cui1, Delong Li1, Xiaomin Zhao1, Wenlong Zhang1, Lingling Chang1, Dewen Tong1

1College of Veterinary Medicine, Northwest A&F University, Xianyang, Shaanxi, P. R. China

*These authors have contributed equally to this work

Correspondence to:

Dewen Tong, e-mail: dwtong@nwsuaf.edu.cn

Keywords: porcine circovirus type 2, capsid, IL-10, gC1qR, Immunology and Microbiology Section, Immune response, Immunity

Received: October 29, 2015     Accepted: January 29, 2016     Published: February 13, 2016


Porcine circovirus type 2 (PCV2) infection caused PCV2-associated diseases (PCVAD) is one of the major emerging immunosuppression diseases in pig industry. In this study, we investigated how PCV2 inoculation increases interleukin (IL)-10 expression in porcine alveolar macrophages (PAMs). PCV2 inoculation significantly upregulated IL-10 expression compared with PCV1. Upon initial PCV2 inoculation, PI3K/Akt cooperated with NF-κB pathways to promote IL-10 transcription via p50, CREB and Ap1 transcription factors, whereas inhibition of PI3K/Akt activation blocked Ap1 and CREB binding to the il10 promoter, and decreased the binding level of NF-κB1 p50 with il10 promoter, leading to great reduction in early IL-10 transcription. In the later phase of inoculation, PCV2 further activated p38 MAPK and ERK pathways to enhance IL-10 production by promoting Sp1 binding to the il10 promoter. For PCV2-induced IL-10 production in macrophages, PCV2 capsid protein Cap, but not the replicase Rep or ORF3, was the critical component. Cap activated PI3K/Akt, p38 MAPK, and ERK signaling pathways to enhance IL-10 expression. In the whole process, gC1qR mediated PCV2-induced PI3K/Akt and p38 MAPK activation to enhance IL-10 induction by interaction with Cap. Depletion of gC1qR blocked PI3K/Akt and p38 MAPK activation, resulting in significant decrease in IL-10 production in PCV2-inoculated cells. Thus, gC1qR might be a critical functional receptor for PCV2-induced IL-10 production. Taken together, these data demonstrated that Cap protein binding with host gC1qR induction of PI3K/Akt and p38 MAPK signalings activation is a critical process in enhancing PCV2-induced IL-10 production in porcine alveolar macrophages.

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