Non-infectious Immune Complexes Downregulate the Production of Interferons and Tumor Necrosis Factor-α in Primary Porcine Alveolar Macrophages

Overview

Journal Front Vet Sci

Specialty Veterinary Medicine

Date 2024 Jul 4

PMID 38962699

Authors

Liujun Zhang

Xing Feng

Weizhen Chen

Bo Wang

Shaojun He

Hongjie Fan

Deyi Liu

Affiliations

Soon will be listed here.

Abstract

Porcine reproductive and respiratory syndrome (PRRS) caused by the PRRS virus (PRRSV) has been harming the pig industry worldwide for nearly 40 years. Although scientific researchers have made substantial efforts to explore PRRSV pathogenesis, the immune factors influencing PRRSV infection still need to be better understood. Infectious virus-antibody immune complexes (ICs) formed by PRRSV and sub-or non-neutralizing antibodies specific for PRRSV may significantly promote the development of PRRS by enhancing PRRSV replication through antibody-dependent enhancement. However, nothing is known about whether PRRSV infection is affected by non-infectious ICs (NICs) formed by non-pathogenic/infectious antigens and corresponding specific antibodies. Here, we found that PRRSV significantly induced the transcripts and proteins of interferon-α (IFN-α), IFN-β, IFN-γ, IFN-λ1, and tumor necrosis factor-α (TNF-α) primary porcine alveolar macrophages (PAMs) in the early stage of infection. Our results showed that NICs formed by rabbit-negative IgG (RNI) and pig anti-RNI specific IgG significantly reduced the transcripts and proteins of IFN-α, IFN-β, IFN-γ, IFN-λ1, and TNF-α PAMs and significantly elevated the transcripts and proteins of interleukine-10 (IL-10) and transforming growth factor-β1 (TGF-β1) PAMs. NICs-mediated PRRSV infection showed that NICs not only significantly decreased the induction of IFN-α, IFN-β, IFN-γ, IFN-λ1, and TNF-α by PRRSV but also significantly increased the induction of IL-10 and TGF-β1 by PRRSV and considerably enhanced PRRSV replication PAMs. Our data suggested that NICs could downregulate the production of antiviral cytokines (IFN-α/β/γ/λ1 and TNF-α) during PRRSV infection and facilitated PRRSV proliferation in its host cells by inhibiting innate antiviral immune response. This study elucidated one novel immune response to PRRSV infection, which would enhance our understanding of the pathogenesis of PRRSV.

References

Kolb P, Giese S, Voll R, Hengel H, Falcone V . Immune complexes as culprits of immunopathology in severe COVID-19. Med Microbiol Immunol. 2022; 212(2):185-191. PMC: 9308473. DOI: 10.1007/s00430-022-00743-8. View

Chen X, Qiao S, Li R, Wang J, Li X, Zhang G . Evasion strategies of porcine reproductive and respiratory syndrome virus. Front Microbiol. 2023; 14:1140449. PMC: 10063791. DOI: 10.3389/fmicb.2023.1140449. View

Nan Y, Wang R, Shen M, Faaberg K, Samal S, Zhang Y . Induction of type I interferons by a novel porcine reproductive and respiratory syndrome virus isolate. Virology. 2012; 432(2):261-70. PMC: 7111977. DOI: 10.1016/j.virol.2012.05.015. View

Gimeno M, Darwich L, Diaz I, de la Torre E, Pujols J, Martin M . Cytokine profiles and phenotype regulation of antigen presenting cells by genotype-I porcine reproductive and respiratory syndrome virus isolates. Vet Res. 2011; 42:9. PMC: 3037899. DOI: 10.1186/1297-9716-42-9. View

Shi P, Zhang L, Wang J, Lu D, Li Y, Ren J . Porcine FcεRI Mediates Porcine Reproductive and Respiratory Syndrome Virus Multiplication and Regulates the Inflammatory Reaction. Virol Sin. 2018; 33(3):249-260. PMC: 6178556. DOI: 10.1007/s12250-018-0032-3. View

Burkard C, Opriessnig T, Mileham A, Stadejek T, Ait-Ali T, Lillico S . Pigs Lacking the Scavenger Receptor Cysteine-Rich Domain 5 of CD163 Are Resistant to Porcine Reproductive and Respiratory Syndrome Virus 1 Infection. J Virol. 2018; 92(16). PMC: 6069206. DOI: 10.1128/JVI.00415-18. View

Khandia R, Munjal A, Dhama K, Karthik K, Tiwari R, Singh Malik Y . Modulation of Dengue/Zika Virus Pathogenicity by Antibody-Dependent Enhancement and Strategies to Protect Against Enhancement in Zika Virus Infection. Front Immunol. 2018; 9:597. PMC: 5925603. DOI: 10.3389/fimmu.2018.00597. View

Zhang H, Guo X, Nelson E, Christopher-Hennings J, Wang X . Porcine reproductive and respiratory syndrome virus activates the transcription of interferon alpha/beta (IFN-α/β) in monocyte-derived dendritic cells (Mo-DC). Vet Microbiol. 2012; 159(3-4):494-8. PMC: 7127654. DOI: 10.1016/j.vetmic.2012.04.025. View

Garcia-Nicolas O, Baumann A, Vielle N, Gomez-Laguna J, Quereda J, Pallares F . Virulence and genotype-associated infectivity of interferon-treated macrophages by porcine reproductive and respiratory syndrome viruses. Virus Res. 2013; 179:204-11. DOI: 10.1016/j.virusres.2013.08.009. View

10.

Taylor A, Foo S, Bruzzone R, Dinh L, King N, Mahalingam S . Fc receptors in antibody-dependent enhancement of viral infections. Immunol Rev. 2015; 268(1):340-64. PMC: 7165974. DOI: 10.1111/imr.12367. View

11.

Han M, Yoo D . Modulation of innate immune signaling by nonstructural protein 1 (nsp1) in the family Arteriviridae. Virus Res. 2014; 194:100-9. PMC: 7114407. DOI: 10.1016/j.virusres.2014.09.007. View

12.

Subramaniam S, Sur J, Kwon B, Pattnaik A, Osorio F . A virulent strain of porcine reproductive and respiratory syndrome virus does not up-regulate interleukin-10 levels in vitro or in vivo. Virus Res. 2010; 155(2):415-22. DOI: 10.1016/j.virusres.2010.11.010. View

13.

Halstead S, Mahalingam S, Marovich M, Ubol S, Mosser D . Intrinsic antibody-dependent enhancement of microbial infection in macrophages: disease regulation by immune complexes. Lancet Infect Dis. 2010; 10(10):712-22. PMC: 3057165. DOI: 10.1016/S1473-3099(10)70166-3. View

14.

Singleton H, Graham S, Bodman-Smith K, Frossard J, Steinbach F . Establishing Porcine Monocyte-Derived Macrophage and Dendritic Cell Systems for Studying the Interaction with PRRSV-1. Front Microbiol. 2016; 7:832. PMC: 4889594. DOI: 10.3389/fmicb.2016.00832. View

15.

Virgin 4th H, Wittenberg G, UNANUE E . Immune complex effects on murine macrophages. I. Immune complexes suppress interferon-gamma induction of Ia expression. J Immunol. 1985; 135(6):3735-43. View

16.

Garcia-Nicolas O, Rosales R, Pallares F, Risco D, Quereda J, Graham S . Comparative analysis of cytokine transcript profiles within mediastinal lymph node compartments of pigs after infection with porcine reproductive and respiratory syndrome genotype 1 strains differing in pathogenicity. Vet Res. 2015; 46:34. PMC: 4364558. DOI: 10.1186/s13567-015-0161-8. View

17.

Chaudhari J, Liew C, Riethoven J, Sillman S, Vu H . Porcine Reproductive and Respiratory Syndrome Virus Infection Upregulates Negative Immune Regulators and T-Cell Exhaustion Markers. J Virol. 2021; 95(21):e0105221. PMC: 8513478. DOI: 10.1128/JVI.01052-21. View

18.

Calzada-Nova G, Schnitzlein W, Husmann R, Zuckermann F . North American porcine reproductive and respiratory syndrome viruses inhibit type I interferon production by plasmacytoid dendritic cells. J Virol. 2010; 85(6):2703-13. PMC: 3067927. DOI: 10.1128/JVI.01616-10. View

19.

Sawant J, Patil A, Kurle S . A Review: Understanding Molecular Mechanisms of Antibody-Dependent Enhancement in Viral Infections. Vaccines (Basel). 2023; 11(7). PMC: 10384352. DOI: 10.3390/vaccines11071240. View

20.

Esparza I, Green R, Schreiber R . Inhibition of macrophage tumoricidal activity by immune complexes and altered erythrocytes. J Immunol. 1983; 131(5):2117-21. View