Distinct functional enrichment of transcriptional signatures in pigs with high and low IFN-gamma responses after vaccination with a porcine reproductive and respiratory syndrome virus (PRRSV).

Tahar Ait-Ali,Enric Mateu,Laila Darwich,Esmeralda Cano,Yanli Li,Alison D Wilson,Alan L Archibald,Ivan Díaz,Bruno Giotti,Ferran Soldevila

doi:10.1186/s13567-016-0392-3

Abstract

Little is known about the host factor in the response to PRRSV vaccination. For this purpose, piglets were immunized with a commercial PRRSV-live vaccine and classified as high responders (HR) or low responders (LR) as regards to the frequencies of virus-specific IFN-γ-secreting cells. Six weeks post vaccination, PBMCs isolated from three individuals with the most extreme responses in each HR and LR groups and 3 unvaccinated controls, were either stimulated with phytohaemagglutinin, challenged with the vaccine or mock treated for 24 h, prior conducting transcriptional studies, gene ontology and pathway analyses. The LR group had very low neutralizing antibody levels and showed a higher number of down-regulated transcripts compared with the HR group (FDR < 0.2, P < 0.001). Down-regulated genes encoded chemoattractants, proinflammatory cytokines and the interferon-inducible GBP family, and showed enrichment in wounding (FDR < 3.6E-13), inflammation (FDR < 8E-12), defence (FDR < 8.7E-09) and immunity (FDR < 7.6E-08), suggesting immune response impairment. In the HR group, down-regulated genes were involved in protein transport (FDR < 4.77E-03), locomotory behavior (FDR < 5.47E-3), regulation of protein localization (FDR < 1.02E-02), and regulation of TNF superfamily member 15 and miR181. In contrast, the HR group presented up-regulated transcripts associated with wounding (FDR < 4.95). Moreover, IFN-γ was predicted to be an inhibited upstream regulator since IFN-γ pathways were associated with higher number of down-regulated genes in the LR (n = 40) than the HR (n = 10). Divergent responses to PRRSV-vaccination may be the result of the genetic background of the host.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-016-0392-3) contains supplementary material, which is available to authorized users.

Highlights

Porcine reproductive and respiratory syndrome (PRRS) is arguably the most endemic infectious disease challenge for the pig industry and causes very significant economic losses worldwide [1, 2]
Characterization of the humoral response in High responder (HR) and Low responder (LR) pigs When the S/P ratios, corresponding to non-neutralizing antibodies (NA), were examined, values were always higher (p < 0.05) in the LR vaccinated group compared to the HR vaccinated group from day 14 PV onwards (Figure 3A)
All animals were negative for PRRS virus (PRRSV) vaccine virus in blood at day 42, with the exception of one animal of the LR group that showed a CT = 35 that corresponds to 1.2–1.3 log10 genomic equivalences per mL

Summary

Introduction

Porcine reproductive and respiratory syndrome (PRRS) is arguably the most endemic infectious disease challenge for the pig industry and causes very significant economic losses worldwide [1, 2]. The most widely used strategy for reducing the incidence and limiting the impact of PRRSV-infection damages is vaccination. Ait‐Ali et al Vet Res (2016) 47:104 on the market but their efficacies are considered to be at best partial as they cannot provide full protection against the wide diversity of PRRSV strains circulating in the field [20, 21]. The genetics of the host (pigs) and of the pathogen (PRRSV) appear to play an important role on the efficacy of vaccination in the control of PRRS

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