In Vitro Analysis of TGF-β Signaling Modulation of Porcine Alveolar Macrophages in Porcine Circovirus Type 2b Infection

Overview

Journal Vet Sci

Publisher MDPI

Specialty Veterinary Medicine

Date 2022 Mar 24

PMID 35324828

Authors

Shunli Yang

Muhammad Umar Zafar Khan

Baohong Liu

Muhammad Humza

Shuanghui Yin

Jianping Cai

Affiliations

Soon will be listed here.

Abstract

Porcine circovirus 2 (PCV2) has been recognized as an immunosuppressive pathogen. However, the crosstalk between this virus and its host cells in related signaling pathways remains poorly understood. In this study, the expression profiles of 84 genes involved in transforming growth factor-beta (TGF-β) signaling pathway were probed in PCV2b-infected primary porcine alveolar macrophages (PAMs) by using an RT profiler PCR array system. The protein expression levels of cytokines involved in the TGF-β signaling pathway were determined with a RayBiotech fluorescent Quantibody porcine cytokine array system. Results showed that 48, 30, and 42 genes were differentially expressed at 1, 24, and 48 h after infection, respectively. A large number of genes analyzed by a co-expression network and implicated in transcriptional regulation and apoptosis were differentially expressed in PCV2b-infected PAMs. Among these genes, TGF-β, interleukin-10, CCAAT/enhancer-binding protein beta (C/EBPB), growth arrest, and DNA-damage-inducible 45 beta (GADD45B), and BCL2 were upregulated. By contrast, SMAD family member 1 (smad1) and smad3 were downregulated. These results suggested that the TGF-β signaling pathway was repressed in PAMs at the early onset of PCV2 infection. The inhibited apoptosis was indicated by the upregulated C/EBPB, GADD45B, and BCL2, and by the downregulated smad1 and smad3, which possibly increased the duration of PCV2 replication-permissive conditions and caused a persistent infection. Our study may provide insights into the underlying antiviral functional changes in the immune system of PCV2-infected pigs.

Citing Articles

Alveolar Macrophages in Viral Respiratory Infections: Sentinels and Saboteurs of Lung Defense.

Popperl P, Stoff M, Beineke A Int J Mol Sci. 2025; 26(1.

PMID: 39796262 PMC: 11721917. DOI: 10.3390/ijms26010407.

Inhibition of YAP1 activity ameliorates acute lung injury through promotion of M2 macrophage polarization.

Liang L, Xu W, Shen A, Fu X, Cen H, Wang S MedComm (2020). 2023; 4(3):e293.

PMID: 37287755 PMC: 10242261. DOI: 10.1002/mco2.293.

The ultrasonically treated nanoliposomes containing PCV2 DNA vaccine expressing gC1qR binding site mutant Cap is efficient in mice.

Du Q, Shi T, Wang H, Zhu C, Yang N, Tong D Front Microbiol. 2023; 13:1077026.

PMID: 36713188 PMC: 9874303. DOI: 10.3389/fmicb.2022.1077026.

TGF-β from the Porcine Intestinal Cell Line IPEC-J2 Induced by Porcine Circovirus 2 Increases the Frequency of Treg Cells via the Activation of ERK (in CD4 T Cells) and NF-κB (in IPEC-J2).

Liu X, Wang Y, Han C, Li Q, Hou X, Song Q Viruses. 2022; 14(11).

PMID: 36366564 PMC: 9698303. DOI: 10.3390/v14112466.

References

Sanchez-Capelo A . Dual role for TGF-beta1 in apoptosis. Cytokine Growth Factor Rev. 2005; 16(1):15-34. DOI: 10.1016/j.cytogfr.2004.11.002. View

Segales J, Rosell C, Domingo M . Pathological findings associated with naturally acquired porcine circovirus type 2 associated disease. Vet Microbiol. 2004; 98(2):137-49. DOI: 10.1016/j.vetmic.2003.10.006. View

Lee H . The Role of Tripartite Motif Family Proteins in TGF-β Signaling Pathway and Cancer. J Cancer Prev. 2019; 23(4):162-169. PMC: 6330992. DOI: 10.15430/JCP.2018.23.4.162. View

Lee G, Han D, Song J, Lee Y, Kang K, Yoon S . Genomic expression profiling in lymph nodes with lymphoid depletion from porcine circovirus 2-infected pigs. J Gen Virol. 2010; 91(Pt 10):2585-91. DOI: 10.1099/vir.0.022608-0. View

Yu S, Opriessnig T, Kitikoon P, Nilubol D, Halbur P, Thacker E . Porcine circovirus type 2 (PCV2) distribution and replication in tissues and immune cells in early infected pigs. Vet Immunol Immunopathol. 2006; 115(3-4):261-72. DOI: 10.1016/j.vetimm.2006.11.006. View

Renukaradhya G, Dwivedi V, Manickam C, Binjawadagi B, Benfield D . Mucosal vaccines to prevent porcine reproductive and respiratory syndrome: a new perspective. Anim Health Res Rev. 2012; 13(1):21-37. DOI: 10.1017/S1466252312000023. View

Shannon P, Markiel A, Ozier O, Baliga N, Wang J, Ramage D . Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003; 13(11):2498-504. PMC: 403769. DOI: 10.1101/gr.1239303. View

Mavrommatis B, Offord V, Patterson R, Watson M, Kanellos T, Steinbach F . Global gene expression profiling of myeloid immune cell subsets in response to in vitro challenge with porcine circovirus 2b. PLoS One. 2014; 9(3):e91081. PMC: 3949749. DOI: 10.1371/journal.pone.0091081. View

Renukaradhya G, Alekseev K, Jung K, Fang Y, Saif L . Porcine reproductive and respiratory syndrome virus-induced immunosuppression exacerbates the inflammatory response to porcine respiratory coronavirus in pigs. Viral Immunol. 2010; 23(5):457-66. PMC: 2967820. DOI: 10.1089/vim.2010.0051. View

10.

Olvera A, Ballester M, Nofrarias M, Sibila M, Aragon V . Differences in phagocytosis susceptibility in Haemophilus parasuis strains. Vet Res. 2009; 40(3):24. PMC: 2695031. DOI: 10.1051/vetres/2009007. View

11.

Darwich L, Mateu E . Immunology of porcine circovirus type 2 (PCV2). Virus Res. 2011; 164(1-2):61-7. DOI: 10.1016/j.virusres.2011.12.003. View

12.

Qin Y, Li H, Qiao J . TLR2/MyD88/NF-κB signalling pathway regulates IL-8 production in porcine alveolar macrophages infected with porcine circovirus 2. J Gen Virol. 2015; 97(2):445-452. DOI: 10.1099/jgv.0.000345. View

13.

Derynck R, Zhang Y . Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 2003; 425(6958):577-84. DOI: 10.1038/nature02006. View

14.

Li C, Ebert P, Li Q . T cell receptor (TCR) and transforming growth factor β (TGF-β) signaling converge on DNA (cytosine-5)-methyltransferase to control forkhead box protein 3 (foxp3) locus methylation and inducible regulatory T cell differentiation. J Biol Chem. 2013; 288(26):19127-39. PMC: 3696685. DOI: 10.1074/jbc.M113.453357. View

15.

Gilpin D, McCullough K, Meehan B, McNeilly F, McNair I, Stevenson L . In vitro studies on the infection and replication of porcine circovirus type 2 in cells of the porcine immune system. Vet Immunol Immunopathol. 2003; 94(3-4):149-61. DOI: 10.1016/s0165-2427(03)00087-4. View

16.

Mandrioli L, Sarli G, Panarese S, Baldoni S, Marcato P . Apoptosis and proliferative activity in lymph node reaction in postweaning multisystemic wasting syndrome (PMWS). Vet Immunol Immunopathol. 2004; 97(1-2):25-37. DOI: 10.1016/j.vetimm.2003.08.017. View

17.

Cory S, Huang D, Adams J . The Bcl-2 family: roles in cell survival and oncogenesis. Oncogene. 2003; 22(53):8590-607. DOI: 10.1038/sj.onc.1207102. View

18.

Ge X, Wang F, Guo X, Yang H . Porcine circovirus type 2 and its associated diseases in China. Virus Res. 2011; 164(1-2):100-6. DOI: 10.1016/j.virusres.2011.10.005. View

19.

Meng X . Spread like a wildfire--the omnipresence of porcine circovirus type 2 (PCV2) and its ever-expanding association with diseases in pigs. Virus Res. 2011; 164(1-2):1-3. DOI: 10.1016/j.virusres.2011.12.005. View

20.

Oh S, Li M . TGF-β: guardian of T cell function. J Immunol. 2013; 191(8):3973-9. PMC: 3856438. DOI: 10.4049/jimmunol.1301843. View