Porcine circovirus type 2 infection inhibits macrophage M1 polarization induced by other pathogens via viral capsid protein and host gC1qR protein

Xuefeng Yang; Qian Du; Xiaofen Wang; Jun Shi; Tongtong Wang; Peixuan Li; Jianhui Zhong; Dewen Tong; Yong Huang

doi:10.1016/j.vetmic.2023.109871

Porcine circovirus type 2 infection inhibits macrophage M1 polarization induced by other pathogens via viral capsid protein and host gC1qR protein

Vet Microbiol. 2023 Oct:285:109871. doi: 10.1016/j.vetmic.2023.109871. Epub 2023 Aug 31.

Authors

Xuefeng Yang¹, Qian Du², Xiaofen Wang¹, Jun Shi¹, Tongtong Wang³, Peixuan Li¹, Jianhui Zhong¹, Dewen Tong⁴, Yong Huang⁵

Affiliations

¹ College of Veterinary Medicine, Northwest A&F University, Yangling, China.
² College of Veterinary Medicine, Northwest A&F University, Yangling, China; Engineering Research Center of Efficient New Vaccines for Animals, Ministry of Education, Yangling, China; Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs, Yangling, China; Engineering Research Center of Efficient New Vaccines for Animals, Universities of Shaanxi Province, Yangling, China.
³ College of Agronomy, Liaocheng University, Liaocheng, China.
⁴ College of Veterinary Medicine, Northwest A&F University, Yangling, China; Engineering Research Center of Efficient New Vaccines for Animals, Ministry of Education, Yangling, China; Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs, Yangling, China; Engineering Research Center of Efficient New Vaccines for Animals, Universities of Shaanxi Province, Yangling, China. Electronic address: dwtong@nwsuaf.edu.cn.
⁵ College of Veterinary Medicine, Northwest A&F University, Yangling, China; Engineering Research Center of Efficient New Vaccines for Animals, Ministry of Education, Yangling, China; Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs, Yangling, China; Engineering Research Center of Efficient New Vaccines for Animals, Universities of Shaanxi Province, Yangling, China. Electronic address: yonghuang@nwsuaf.edu.cn.

PMID: 37672899
DOI: 10.1016/j.vetmic.2023.109871

Abstract

Porcine circovirus type 2 (PCV2) has been proven to co-infect with a variety of pathogens and cause immunosuppression. Previously, we have reported that PCV2 infection attenuates the production of pro-inflammatory cytokines induced by other pathogens in porcine macrophages. However, whether PCV2 can affect M1-type macrophage polarization induced by other pathogens is less well reported. Herein, we found that PCV2 infection suppressed M1 macrophage production induced by porcine reproductive and respiratory syndrome virus (PRRSV) and Haemophilus parasuis (H. parasuis) in the lung and promoted the proliferation of these pathogens in the piglets. Consistently, we confirmed that PCV2 inhibits M1 macrophage production and its associated gene expression in porcine alveolar macrophages (PAMs) both ex vivo and in vitro. Meanwhile, PCV2 inhibited lipopolysaccharide (LPS)-induced pro-inflammatory cytokines in vitro in a time- and dose-dependent manner. In PCV2-infected cells, LPS-induced signal transducer and activator of transcription (STAT1) phosphorylation and its nuclear translocation were decreased. Based on these findings, we further identified a role for PCV2 capsid protein (Cap) in LPS-induced M1 macrophage-associated genes and found that PCV2 Cap can significantly reduce STAT1 phosphorylation and its nuclear translocation, as well as the production of M1 macrophage-related genes. As the binding protein of PCV2 Cap, gC1qR protein was also associated with this inhibition process. gC1qR-binding activity-deficient PCV2 Cap mutated protein (Cap RmA) appeared an attenuated inhibitory effect on other pathogen-induced polarization of M1-type macrophages, suggesting that the inhibitory effect of PCV2 infection on M1-type macrophage polarization induced by other pathogens is dependent on Cap protein and the host gC1qR protein. Altogether, our results demonstrate that PCV2 infection inhibits macrophage M1 polarization induced by other pathogens via capsid and host gC1qR protein modulating JAK/STAT signaling.

Keywords: Capsid; JAK-STAT pathway; M1 polarization; Porcine circovirus type 2 (PCV2); Pro-inflammatory; gC1qR.