Impact of genotype 1 and 2 of porcine reproductive and respiratory syndrome viruses on interferon-α responses by plasmacytoid dendritic cells

Arnaud Baumann,Enric Mateu,Michael P Murtaugh,Artur Summerfield

doi:10.1186/1297-9716-44-33

Arnaud Baumann, Enric Mateu + Show 2 more

Open Access

https://doi.org/10.1186/1297-9716-44-33

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Abstract

Porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) infections are characterized by prolonged viremia and viral shedding consistent with incomplete immunity. Type I interferons (IFN) are essential for mounting efficient antiviral innate and adaptive immune responses, but in a recent study, North American PRRSV genotype 2 isolates did not induce, or even strongly inhibited, IFN-α in plasmacytoid dendritic cells (pDC), representing “professional IFN-α-producing cells”. Since inhibition of IFN-α expression might initiate PRRSV pathogenesis, we further characterized PRRSV effects and host modifying factors on IFN-α responses of pDC. Surprisingly, a variety of type 1 and type 2 PRRSV directly stimulated IFN-α secretion by pDC. The effect did not require live virus and was mediated through the TLR7 pathway. Furthermore, both IFN-γ and IL-4 significantly enhanced the pDC production of IFN-α in response to PRRSV exposure. PRRSV inhibition of IFN-α responses from enriched pDC stimulated by CpG oligodeoxynucleotides was weak or absent. VR-2332, the prototype genotype 2 PRRSV, only suppressed the responses by 34%, and the highest level of suppression (51%) was induced by a Chinese highly pathogenic PRRSV isolate. Taken together, these findings demonstrate that pDC respond to PRRSV and suggest that suppressive activities on pDC, if any, are moderate and strain-dependent. Thus, pDC may be a source of systemic IFN-α responses reported in PRRSV-infected animals, further contributing to the puzzling immunopathogenesis of PRRS.

Highlights

Type I interferons (IFN), mainly IFN-α/β, are essential to the innate immune system for direct antiviral activity as well as efficient induction of adaptive immune responses [1,2]
To further investigate if Plasmacytoid dendritic cells (pDC) production of IFN-α was a universal response to PRRSV, type 2 strains VR-2332, JA-1262, a virulent recent USA field isolate, SY0608, a highly pathogenic field isolate from China, and the avirulent type 1 Olot/91 strain were incubated with enriched pDC
Whereas no or only low levels of IFN-α were found in peripheral blood mononuclear cells (PBMC) after PRRSV exposure (Figure 1D), high amounts were detected in the CD14-CD4+ cell fraction (Figure 1E)

Summary

Introduction

Type I interferons (IFN), mainly IFN-α/β, are essential to the innate immune system for direct antiviral activity as well as efficient induction of adaptive immune responses [1,2]. PDC are a rare cell type, they can produce around 100 times more IFN-α than any other cellular type They are often able to sense viruses in the absence of viral replication. They represent an important candidate cell type for investigating early immune events that could influence early control of virus replication or induction of adaptive antiviral immune response [22]. In the pig, these cells have been identified as CD4+CD123+CD135+CD172a +CD14-, which can be differentiated from monocytes, macrophages and MoDC which lack CD4, CD123 and CD135 but express CD14 and in the case of macrophages and monocyte subset CD163 [23,24]. Considering the observation of in vivo IFN-α, important differences in the virulence of genotype 1 and genotype 2, and the possible regulation of pDC responses by cytokines induced during PRRS infection, we examined how PRRSV of different genotypes and virulence interact with pDC and how cytokines influence pDC responses

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