title: Porcine circovirus type 2 activates PI3K/Akt and p38 MAPK pathways to promote interleukin-10 production in macrophages via Cap interaction of gC1qR.
abstract: 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.
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Xianyang, Shaanxi, P. R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Du
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Xianyang, Shaanxi, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Xianyang, Shaanxi, P. R. China.
authors.forename: Tongtong
authors.initials: T
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Xianyang, Shaanxi, P. R. China.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Xianyang, Shaanxi, P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Xianyang, Shaanxi, P. R. China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Cui
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Xianyang, Shaanxi, P. R. China.
authors.forename: Delong
authors.initials: D
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Xianyang, Shaanxi, P. R. China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Xianyang, Shaanxi, P. R. China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Xianyang, Shaanxi, P. R. China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Chang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Xianyang, Shaanxi, P. R. China.
authors.forename: Dewen
authors.initials: D
authors.lastname: Tong
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002460:Cell Line; D018173:Circoviridae Infections / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D017925:Circovirus / Q000276:immunology / Q000378:metabolism*; D015922:Complement C1q / Q000378:metabolism*; D055786:Gene Knockout Techniques; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D020935:MAP Kinase Signaling System; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000276:immunology; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011951:Receptors, Complement / Q000276:immunology; D015398:Signal Transduction; D013552:Swine; D013553:Swine Diseases / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000914:Antibodies, Viral; D008562:Membrane Glycoproteins; D011951:Receptors, Complement; C032402:complement 1q receptor; D016753:Interleukin-10; D015922:Complement C1q; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D048051:p38 Mitogen-Activated Protein Kinases
keywords: IL-10; Immune response; Immunity; Immunology and Microbiology Section; capsid; gC1qR; porcine circovirus type 2