Abstract
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.
Highlights
In 2009, the swine-origin H1N1 influenza A virus (IAV) emerged and caused outbreaks of respiratory illness in humans around the world
Three main mechanisms are suggested to be involved in pandemic H1N1 (pH1N1) pathogenicity: (i) alveolar epithelial necrosis, caused by viral cytopathogenicity, and the release of cytokines by infected cells; (ii) activation of lung vasculature, which increases endothelial permeability, releases cytokines, and triggers leukocyte migration; and (iii) damage triggered by the inflammatory infiltrates, mainly formed by neutrophils and macrophages, plus the release of cytokines from these cells [10]
Inflammation was firstly observed in bronchiolar compartments, in association with viral replication in bronchiolar epithelial cells and the higher expression of IFNα and IL-6, early after infection
Summary
In 2009, the swine-origin H1N1 influenza A virus (IAV) emerged and caused outbreaks of respiratory illness in humans around the world. After the 2009 pandemic, outbreaks of that strain have continued to cause serious illness and increased mortality, in young adults and children [1]. The physiopathology of pandemic H1N1 (pH1N1) infection differs between individuals. Whilst most patients develop mild upper respiratory-tract infection [2], some patients progress to develop severe lower respiratory tract complications [3]. High rates of clinically unapparent infections have been reported by seroepidemiological studies [4, 5]. This evidence suggests that the severity of influenza is, at least, partially determined by host factors
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