PMID- 37672899
OWN - NLM
STAT- Publisher
LR  - 20230929
IS  - 1873-2542 (Electronic)
IS  - 0378-1135 (Linking)
VI  - 285
DP  - 2023 Oct
TI  - Porcine circovirus type 2 infection inhibits macrophage M1 polarization induced 
      by other pathogens via viral capsid protein and host gC1qR protein.
PG  - 109871
LID - S0378-1135(23)00223-7 [pii]
LID - 10.1016/j.vetmic.2023.109871 [doi]
AB  - 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.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Yang, Xuefeng
AU  - Yang X
AD  - College of Veterinary Medicine, Northwest A&F University, Yangling, China.
FAU - Du, Qian
AU  - Du Q
AD  - 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.
FAU - Wang, Xiaofen
AU  - Wang X
AD  - College of Veterinary Medicine, Northwest A&F University, Yangling, China.
FAU - Shi, Jun
AU  - Shi J
AD  - College of Veterinary Medicine, Northwest A&F University, Yangling, China.
FAU - Wang, Tongtong
AU  - Wang T
AD  - College of Agronomy, Liaocheng University, Liaocheng, China.
FAU - Li, Peixuan
AU  - Li P
AD  - College of Veterinary Medicine, Northwest A&F University, Yangling, China.
FAU - Zhong, Jianhui
AU  - Zhong J
AD  - College of Veterinary Medicine, Northwest A&F University, Yangling, China.
FAU - Tong, Dewen
AU  - Tong D
AD  - 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.
FAU - Huang, Yong
AU  - Huang Y
AD  - 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.
LA  - eng
PT  - Journal Article
DEP - 20230831
PL  - Netherlands
TA  - Vet Microbiol
JT  - Veterinary microbiology
JID - 7705469
SB  - IM
OTO - NOTNLM
OT  - Capsid
OT  - JAK-STAT pathway
OT  - M1 polarization
OT  - Porcine circovirus type 2 (PCV2)
OT  - Pro-inflammatory
OT  - gC1qR
COIS- Declaration of Competing Interest The authors declare that they have no competing 
      interests. All authors declare that the research was conducted in the absence of 
      any commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/09/07 00:41
MHDA- 2023/09/07 00:41
CRDT- 2023/09/06 18:10
PHST- 2023/07/20 00:00 [received]
PHST- 2023/08/28 00:00 [revised]
PHST- 2023/08/29 00:00 [accepted]
PHST- 2023/09/07 00:41 [pubmed]
PHST- 2023/09/07 00:41 [medline]
PHST- 2023/09/06 18:10 [entrez]
AID - S0378-1135(23)00223-7 [pii]
AID - 10.1016/j.vetmic.2023.109871 [doi]
PST - ppublish
SO  - Vet Microbiol. 2023 Oct;285:109871. doi: 10.1016/j.vetmic.2023.109871. Epub 2023 
      Aug 31.