Regulation of Porcine Plasmacytoid Dendritic Cells by Cytokines

Lannes, Nils; Summerfield, Artur

doi:10.1371/journal.pone.0060893

Cited by 8 publications

(6 citation statements)

References 40 publications

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“…The regulatory cytokine IL-10 was thought to strongly impact PRRSV pathogenesis and was one of the proposed mechanisms used by PRRSV to escape the innate and adaptive immune system. However, the induction of IL-10 by PRRSV is not clearly established [11,51], although its presence suppresses type I IFN induction in pDC [52,53]. It has been reported that PRRSV could induce IL-4 in the serum [20] and IFN-γ both in the serum [54] and in the lungs [48] of infected pigs.…”

Section: Discussionmentioning

confidence: 99%

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

Baumann

Mateu

Murtaugh

et al. 2013

Vet Res

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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.

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Section: Discussionmentioning

confidence: 99%

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

Baumann

Mateu

Murtaugh

et al. 2013

Vet Res

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“…DCs are the most potent antigen-presenting cells (APCs), whose function is to initiate an adaptive immune response. Activation and maturation of DCs are induced by infectious agents and inflammatory products [7] , [30] , as well as by host cytokines [31] , [32] . Cytokines affect DC differentiation and are important in controlling states of perpetual inflammation, as can be seen in CP, when DCs are continuously exposed to antigens [33] .…”

Section: Discussionmentioning

confidence: 99%

Pro-inflammatory, Th1, Th2, Th17 Cytokines and Dendritic Cells: A Cross-sectional Study in Chronic Periodontitis

et al. 2014

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There are a limited number of studies correlating the different stages of dendritic cells (DC) maturation with cytokines in individuals presented chronic periodontitis (CP). The aim of the study was to evaluate the correlation among the expression of IL-2, IL-10, IL-4, IL-6, IFN-, TNF-α, and IL-17A with the presence of DC and mild-moderate or advanced CP. Gingival samples were obtained from 24 individuals with CP and six samples of normal mucosa (NM) overlapping third molar for controls of the levels of cytokines. Periodontal examination was performed. Immunohistochemical staining was carried out, revealing CD1a+ immature, Fator XIIIa+ immature, and CD83+ mature DCs. The inflammatory infiltrate was counted, and the cytokines were measured by flow cytometry. Densities of DCs and inflammatory infiltrate, cytokines, subtypes of CP, and clinical periodontal parameters were correlated and compared. IL-6 expression was correlated positively with the increased numbers of CD1a+ immature DCs. Levels of IL-2, TNF-α, IFN-, IL-10, and IL-17A were increased when compared with NM. The percentage of sites with clinical attachment level (CAL)>3 were positively correlated with densities of inflammatory infiltrate and negatively correlated with densities of immature DCs. IL-6 can contribute to the increase of the immature DCs in the CP. Higher levels of IL-2, TNF-α, IFN-, IL-10, and IL-17A cytokines were observed in CP. Higher densities of inflammatory infiltrate as well as lower densities of immature DCs can result in a more severe degree of human CP.

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“…For opsonization assays, we made use of a previously established assay based on the ability of plasmacytoid dendritic cells (pDCs) to secrete enhanced INF-α in response to immune complexed virus compared with free virus via an Fcγ receptors (FcγR)-dependent pathway ( 19 – 21 ). To this end, peripheral blood mononuclear cells (PBMCs) were freshly isolated from blood of our SPF pigs using ficoll-paque density centrifugation (1.077 g/l, Amersham Pharmacia Biotech).…”

Section: Methodsmentioning

confidence: 99%

Partial Protection against Porcine Influenza A Virus by a Hemagglutinin-Expressing Virus Replicon Particle Vaccine in the Absence of Neutralizing Antibodies

Ricklin¹,

Vielle²,

Python³

et al. 2016

Front. Immunol.

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This work was initiated by previous reports demonstrating that mismatched influenza A virus (IAV) vaccines can induce enhanced disease, probably mediated by antibodies. Our aim was, therefore, to investigate if a vaccine inducing opsonizing but not neutralizing antibodies against the hemagglutinin (HA) of a selected heterologous challenge virus would enhance disease or induce protective immune responses in the pig model. To this end, we immunized pigs with either whole inactivated virus (WIV)-vaccine or HA-expressing virus replicon particles (VRP) vaccine based on recombinant vesicular stomatitis virus (VSV). Both types of vaccines induced virus neutralizing and opsonizing antibodies against homologous virus as shown by a highly sensitive plasmacytoid dendritic cell-based opsonization assay. Opsonizing antibodies showed a broader reactivity against heterologous IAV compared with neutralizing antibodies. Pigs immunized with HA-recombinant VRP vaccine were partially protected from infection with a mismatched IAV, which was not neutralized but opsonized by the immune sera. The VRP vaccine reduced lung lesions, lung inflammatory cytokine responses, serum IFN-α responses, and viral loads in the airways. Only the VRP vaccine was able to prime IAV-specific IFNγ/TNFα dual secreting CD4+ T cells detectable in the peripheral blood. In summary, this work demonstrates that with the virus pair selected, a WIV vaccine inducing opsonizing antibodies against HA which lack neutralizing activity, is neither protective nor does it induce enhanced disease in pigs. In contrast, VRP-expressing HA is efficacious vaccines in swine as they induced both potent antibodies and T-cell immunity resulting in a broader protective value.

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Regulation of Porcine Plasmacytoid Dendritic Cells by Cytokines

Cited by 8 publications

References 40 publications

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

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

Pro-inflammatory, Th1, Th2, Th17 Cytokines and Dendritic Cells: A Cross-sectional Study in Chronic Periodontitis

Partial Protection against Porcine Influenza A Virus by a Hemagglutinin-Expressing Virus Replicon Particle Vaccine in the Absence of Neutralizing Antibodies

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