Endothelial activation and dysfunction in the pathogenesis of influenza A virus infection

Armstrong, Susan; Darwish, Ilyse; Lee, Warren L.

doi:10.4161/viru.25779

Cited by 96 publications

(88 citation statements)

References 68 publications

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“…Supporting this hypothesis, replication-deficient IAV, arisen from internal deletions of IAVs, significantly activated endothelial lung cells inducing a strong host cell response [52]. Besides, it has been recently proved, in vitro and in vivo, that various types of non-self eRNA can be sensed by recipient cells during infection, inducing the release of pro-inflammatory cytokines from recipient cells [17, 53–55]. …”

Section: Discussionmentioning

confidence: 99%

Involvement of the different lung compartments in the pathogenesis of pH1N1 influenza virus infection in ferrets

Vidaña

Martínez

Martorell

et al. 2016

Vet Res

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Severe cases after pH1N1 infection are consequence of interstitial pneumonia triggered by alveolar viral replication and an exacerbated host immune response, characterized by the up-regulation of pro-inflammatory cytokines and the influx of inflammatory leukocytes to the lungs. Different lung cell populations have been suggested as culprits in the unregulated innate immune responses observed in these cases. This study aims to clarify this question by studying the different induction of innate immune molecules by the distinct lung anatomic compartments (vascular, alveolar and bronchiolar) of ferrets intratracheally infected with a human pH1N1 viral isolate, by means of laser microdissection techniques. The obtained results were then analysed in relation to viral quantification in the different anatomic areas and the histopathological lesions observed. More severe lung lesions were observed at 24 h post infection (hpi) correlating with viral antigen detection in bronchiolar and alveolar epithelial cells. However, high levels of viral RNA were detected in all anatomic compartments throughout infection. Bronchiolar areas were the first source of IFN-α and most pro-inflammatory cytokines, through the activation of RIG-I. In contrast, vascular areas contributed with the highest induction of CCL2 and other pro-inflammatory cytokines, through the activation of TLR3.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-016-0395-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Involvement of the different lung compartments in the pathogenesis of pH1N1 influenza virus infection in ferrets

Vidaña

Martínez

Martorell

et al. 2016

Vet Res

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“…Resting ECs avoid the inappropriate plug formation by controlling platelet adhesion and activation and generating several anticoagulant factors providing a non-thrombogenic barrier (55, 56). Once activated or injured, ECs expose collagen to blood, increase platelet binding and aggregation, reduce the expression physiological anticoagulant factors, increase the expression of TF and von willebrand factor, and suppress the fibrinolytic activity (57, 58). All these changes in the hemostatic system facilitate thrombosis in the infected or inflammated tissue.…”

Section: Respiratory Immune-coagulative Response and Ifvmentioning

confidence: 99%

Respiratory Antiviral Immunity and Immunobiotics: Beneficial Effects on Inflammation-Coagulation Interaction during Influenza Virus Infection

et al. 2016

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Influenza virus (IFV) is a major respiratory pathogen of global importance, and the cause of a high degree of morbidity and mortality, especially in high-risk populations such as infants, elderly, and immunocompromised hosts. Given its high capacity to change antigenically, acquired immunity is often not effective to limit IFV infection and therefore vaccination must be constantly redesigned to achieve effective protection. Improvement of respiratory and systemic innate immune mechanisms has been proposed to reduce the incidence and severity of IFV disease. In the last decade, several research works have demonstrated that microbes with the capacity to modulate the mucosal immune system (immunobiotics) are a potential alternative to beneficially modulate the outcome of IFV infection. This review provides an update of the current status on the modulation of respiratory immunity by orally and nasally administered immunobiotics, and their beneficial impact on IFV clearance and inflammatory-mediated lung tissue damage. In particular, we describe the research of our group that investigated the influence of immunobiotics on inflammation–coagulation interactions during IFV infection. Studies have clearly demonstrated that hostile inflammation is accompanied by dysfunctional coagulation in respiratory IFV disease, and our investigations have proved that some immunobiotic strains are able to reduce viral disease severity through their capacity to modulate the immune-coagulative responses in the respiratory tract.

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“…In addition to epithelial cells, there is a growing body of evidence that endothelial cells also play an important role in IAV-induced oedema and alveolitis [10][11][12]. For example, in mice, endothelial cells have been identified as the key drivers of the "cytokine storm" observed during severe IAV infections [11].…”

Section: Introductionmentioning

confidence: 99%

Influenza virus damages the alveolar barrier by disrupting epithelial cell tight junctions

Short

Kasper

Aa³

et al. 2016

Eur Respir J

177

158

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A major cause of respiratory failure during influenza A virus (IAV) infection is damage to the epithelial-endothelial barrier of the pulmonary alveolus. Damage to this barrier results in flooding of the alveolar lumen with proteinaceous oedema fluid, erythrocytes and inflammatory cells. To date, the exact roles of pulmonary epithelial and endothelial cells in this process remain unclear.Here, we used an in vitro co-culture model to understand how IAV damages the pulmonary epithelialendothelial barrier. Human epithelial cells were seeded on the upper half of a transwell membrane while human endothelial cells were seeded on the lower half. These cells were then grown in co-culture and IAV was added to the upper chamber.We showed that the addition of IAV (H1N1 and H5N1 subtypes) resulted in significant barrier damage. Interestingly, we found that, while endothelial cells mounted a pro-inflammatory/pro-coagulant response to a viral infection in the adjacent epithelial cells, damage to the alveolar epithelial-endothelial barrier occurred independently of endothelial cells. Rather, barrier damage was associated with disruption of tight junctions amongst epithelial cells, and specifically with loss of tight junction protein claudin-4.Taken together, these data suggest that maintaining epithelial cell integrity is key in reducing pulmonary oedema during IAV infection. @ERSpublications Influenza A virus damages tight junctions, and specifically claudin-4, of respiratory epithelial cells

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Endothelial activation and dysfunction in the pathogenesis of influenza A virus infection

Cited by 96 publications

References 68 publications

Involvement of the different lung compartments in the pathogenesis of pH1N1 influenza virus infection in ferrets

Involvement of the different lung compartments in the pathogenesis of pH1N1 influenza virus infection in ferrets

Respiratory Antiviral Immunity and Immunobiotics: Beneficial Effects on Inflammation-Coagulation Interaction during Influenza Virus Infection

Influenza virus damages the alveolar barrier by disrupting epithelial cell tight junctions

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