Impaired virus‐induced interferon‐α2 release in adult asthmatic patients

Gehlhar, Kirsten; Bilitewski, C.; Reinitz-Rademacher, K.; Rohde, Gernot; Bufe, Albrecht

doi:10.1111/j.1365-2222.2006.02450.x

Cited by 90 publications

(90 citation statements)

References 30 publications

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“…An inverse correlation between IFN-c production and viral load and/or symptoms score has been documented [81]. In the same context, PBMCs from asthmatic patients were reported to produce less IFN-a2 than PBMCs from normal controls in response to RSV and Newcastle virus infection, also implicating IFN-a in the pathogenesis of asthma exacerbations [82].…”

Section: Mechanisms Of Virus-induced Exacerbationmentioning

confidence: 95%

Childhood asthma and infection: virus-induced exacerbations as determinants and modifiers: Figure 1–

Xepapadaki¹,

Papadopoulos²

2010

Eur Respir J

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Respiratory infections have been implicated in the origin and exacerbation of asthma in a variety of ways; however, systemisation of this knowledge in a way helpful for disease management remains suboptimal.Several conceptual issues need to be taken into account: the fact that the effects of an infection may vary according to genetic background, the current immune status of the host, and parallel environmental stimuli, in addition to the particular infectious agent itself. Moreover, childhood is a very special period because of the continuous processes taking place, such as neural, immune and respiratory maturation.Epidemiological studies have convincingly demonstrated that the majority of asthma exacerbations, in both adults and children, follow viral upper respiratory tract infections. Asthma exacerbations are still often unresponsive to current asthma treatment, and new therapeutic approaches are required.This review presents current knowledge on the associations between infection and exacerbation of established asthma with respect to definitions, epidemiology, mechanisms and treatment.

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Section: Mechanisms Of Virus-induced Exacerbationmentioning

confidence: 95%

Childhood asthma and infection: virus-induced exacerbations as determinants and modifiers: Figure 1–

Xepapadaki¹,

Papadopoulos²

2010

Eur Respir J

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“…The findings of the current study shed light on potential mechanisms by which this might occur. Evidence for deficient IFN-ab secretion in asthma relative to healthy subjects has arisen from studies using different viruses and various circulating cell populations, including bronchial epithelial cells (8), PBMC (12,19), and purified pDC (17). Asthma is also associated with numerical changes in circulating pDC, with lower numbers of blood pDC reported in infants and children (15,40), although studies in adult asthma suggest that blood pDC numbers may be increased (16).…”

Section: Discussionmentioning

confidence: 99%

“…RV-stimulated alveolar macrophages from asthmatics produce less IFN-l than alveolar macrophages from healthy individuals (7). PBMC from asthmatic children and adults secrete less IFN-a following in vitro exposure to viruses (11,12), and this is associated with reduced function of TLR7, the receptor for viral ssRNA (13). Plasmacytoid dendritic cells (pDC) are a potent source of type-I IFN synthesis during virus infections (14), and numerical changes in circulating pDC have been linked both to asthma development in young children (15) and to established asthma in adults (16).…”

mentioning

confidence: 99%

Innate IFNs and Plasmacytoid Dendritic Cells Constrain Th2 Cytokine Responses to Rhinovirus: A Regulatory Mechanism with Relevance to Asthma

Pritchard

Carroll

Burel

et al. 2012

The Journal of Immunology

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Human rhinoviruses (RV) cause only minor illness in healthy individuals, but can have deleterious consequences in people with asthma. This study sought to examine normal homeostatic mechanisms regulating adaptive immunity to RV in healthy humans, focusing on effects of IFN-αβ and plasmacytoid dendritic cells (pDC) on Th2 immune responses. PBMC were isolated from 27 healthy individuals and cultured with RV16 for up to 5 d. In some experiments, IFN-αβ was neutralized using a decoy receptor that blocks IFN signaling, whereas specific dendritic cell subsets were depleted from cultures with immune-magnetic beads. RV16 induced robust expression of IFN-α, IFN-β, multiple IFN-stimulated genes, and T cell-polarizing factors within the first 24 h. At 5 d, the production of memory T cell-derived IFN-γ, IL-10, and IL-13, but not IL-17A, was significantly elevated. Neutralizing the effects of type-I IFN with the decoy receptor B18R led to a significant increase in IL-13 synthesis, but had no effect on IFN-γ synthesis. Depletion of pDC from RV-stimulated cultures markedly inhibited IFN-α secretion, and led to a significant increase in expression and production of the Th2 cytokines IL-5 (p = 0.02), IL-9 (p < 0.01), and IL-13 (p < 0.01), but had no effect on IFN-γ synthesis. Depletion of CD1c+ dendritic cells did not alter cytokine synthesis. In healthy humans, pDC and the IFN-αβ they secrete selectively constrain Th2 cytokine synthesis following RV exposure in vitro. This important regulatory mechanism may be lost in asthma; deficient IFN-αβ synthesis and/or pDC dysfunction have the potential to contribute to asthma exacerbations during RV infections.

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“…It is noted, however, that iloprost was able to suppress TLR-mediated induction of another regulatory cytokine, IFN-a, in pDCs. IFN-a from pDCs has been suggested to play a role in conferring the protective effect in pulmonary allergic inflammation and, in fact, significantly lower amounts of virus-induced IFN-a is seen in allergic asthmatic patients when compared with healthy children or those with intrinsic asthma [21]. Further work is, thus, required to evaluate the potential use of iloprost and/or IP agonists in asthma.…”

Section: Discussionmentioning

confidence: 99%

Regulation of cytokine expression in human plasmacytoid dendritic cells by prostaglandin I₂analogues

Yt²,

Jl³

et al. 2009

Eur Respir J

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Plasmacytoid dendritic cells (pDCs) are critical in controlling adaptive immunity, but the mechanisms governing cytokine expression remain incompletely defined. Analogues of prostaglandin (PG)I 2 , such as iloprost, can modulate functions of myeloid dendritic cells, but their involvement in the regulation of human pDCs remains unknown. To this end, the regulatory role of PGI 2 analogues on cytokine expression in pDCs was investigated.Circulating pDCs were magnetically sorted with BDCA-4 cell isolation kits from human peripheral blood mononuclear cells and treated with varying concentrations of iloprost with or without the addition of Toll-like receptor agonists, or an I prostanoid (IP) receptor antagonist, CAY10449. The levels of tumour necrosis factor (TNF)-a, interferon (IFN)-a and interleukin (IL)-10 were measured by ELISA.Iloprost induced IL-10 expression, but suppressed CpG oligodeoxynucleotide-(or imiquimod-) induced TNF-a and IFN-a production in pDCs. This effect was reversed by the addition of CAY10449. Forskolin, a cyclic adenosine monophosphate activator, conferred a similar modulating effect to that noted in iloprost-treated pDCs, although a higher concentration of forskolin was required to exert the same effect.Iloprost enhanced interleukin-10 and suppressed Toll-like receptor-mediated tumour necrosis factor-a and interferon-a production of human plasmacytoid dendritic cells via the I prostanoid receptor and, in part, the cyclic adenosine monophosphate pathway.

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Impaired virus‐induced interferon‐α2 release in adult asthmatic patients

Cited by 90 publications

References 30 publications

Childhood asthma and infection: virus-induced exacerbations as determinants and modifiers: Figure 1–

Childhood asthma and infection: virus-induced exacerbations as determinants and modifiers: Figure 1–

Innate IFNs and Plasmacytoid Dendritic Cells Constrain Th2 Cytokine Responses to Rhinovirus: A Regulatory Mechanism with Relevance to Asthma

Regulation of cytokine expression in human plasmacytoid dendritic cells by prostaglandin I₂analogues

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Impaired virus‐induced interferon‐α2 release in adult asthmatic patients

Cited by 90 publications

References 30 publications

Childhood asthma and infection: virus-induced exacerbations as determinants and modifiers: Figure 1–

Childhood asthma and infection: virus-induced exacerbations as determinants and modifiers: Figure 1–

Innate IFNs and Plasmacytoid Dendritic Cells Constrain Th2 Cytokine Responses to Rhinovirus: A Regulatory Mechanism with Relevance to Asthma

Regulation of cytokine expression in human plasmacytoid dendritic cells by prostaglandin I2analogues

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Regulation of cytokine expression in human plasmacytoid dendritic cells by prostaglandin I₂analogues