IL1RL1 Gene Variants and Nasopharyngeal IL1RL-a Levels Are Associated with Severe RSV Bronchiolitis: A Multicenter Cohort Study

Faber, Tina E; Schuurhof, Annemieke; Vonk, Annelies; Koppelman, Gerard H.; Hennus, Marije P.; Kimpen, Jan L. L.; Janssen, Riny; Bont, Louis

doi:10.1371/journal.pone.0034364

Cited by 37 publications

(44 citation statements)

References 37 publications

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“…In addition, a recent clinical multicenter cohort study found that human IL1RL1 gene variants and nasopharyngeal IL1RL1-a levels were associated with severe RSV bronchiolitis. The potential biological role of IL1RL1 in the pathogenesis of severe RSV bronchiolitis was supported by high local concentrations of IL1RL1 in children with the most severe disease (16). An important genetic association linking RV with asthma has been identified between host 17q21 locus variants and RV wheezing illness (17).…”

Section: Host Genetic and Familial Determinants Linking Infant Rsv Anmentioning

confidence: 99%

“…The GA3 clade has been associated with greater severity of illness compared with clades GA2 and GA4 (41). Differential pathogenesis of RSV A subgroup strains has been reported in an animal model of infection of BALB/cJ mice with RSV A2001/2-20 (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). A subgroup strain resulted in greater disease severity, higher lung IL-13 levels, and higher lung gob-5 levels and induced airway mucin expression, supporting differential pathogenicity dependent on strain in these genetically identical mice (42).…”

Section: Viral Strain Determinants Of Infant Infection Severity and Amentioning

confidence: 99%

See 1 more Smart Citation

Toward Primary Prevention of Asthma. Reviewing the Evidence for Early-Life Respiratory Viral Infections as Modifiable Risk Factors to Prevent Childhood Asthma

Feldman

Moore

et al. 2015

Am J Respir Crit Care Med

173

172

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A first step in primary disease prevention is identifying common, modifiable risk factors that contribute to a significant proportion of disease development. Infant respiratory viral infection and childhood asthma are the most common acute and chronic diseases of childhood, respectively. Common clinical features and links between these diseases have long been recognized, with early-life respiratory syncytial virus (RSV) and rhinovirus (RV) lower respiratory tract infections (LRTIs) being strongly associated with increased asthma risk. However, there has long been debate over the role of these respiratory viruses in asthma inception. In this article, we systematically review the evidence linking early-life RSV and RV LRTIs with asthma inception and whether they could therefore be targets for primary prevention efforts.

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Section: Host Genetic and Familial Determinants Linking Infant Rsv Anmentioning

confidence: 99%

Section: Viral Strain Determinants Of Infant Infection Severity and Amentioning

confidence: 99%

Toward Primary Prevention of Asthma. Reviewing the Evidence for Early-Life Respiratory Viral Infections as Modifiable Risk Factors to Prevent Childhood Asthma

Feldman

Moore

et al. 2015

Am J Respir Crit Care Med

173

172

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“…Genetic variation at a number of different loci also contribute to the frequency and severity of the host response to viral infection. 15-18 Finally, the socioeconomic environment may also contribute. 2012 studies showing comparisons of the viral etiology during infancy in children living in the inner-cities of the USA compared to a more suburban environment revealed some interesting differences.…”

Section: Demographicsmentioning

confidence: 99%

“…18 Polymorphisms in IL10, chemokine receptor 5, transforming growth factor β, TLR4, IL13, IL4, and IL-4RA genes are associated with RSV induced bronchiolitis severity. 15 …”

Section: Biomarkersmentioning

confidence: 99%

Infection-Related Asthma

Darveaux

Lemanske

2014

The Journal of Allergy and Clinical Immunology: In Practice

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The role of infection in asthma is varied in that it may exacerbate established asthma or contribute to the initial development of the clinical onset of asthma. Mounting evidence implicates both roles, with particular viral pathogens, namely human rhinovirus (HRV) and respiratory syncytial virus (RSV), among the most likely culprits in asthma inception. Once asthma is present, infection, particularly viral infections, are a common precipitant of asthma exacerbations. Bacterial infections and colonization also have been associated with exacerbation and recurrent wheeze, an effect that may be independent or a cofactor with viruses. Atypical bacterial infections such as Mycoplasma pneumoniae and Chlamydia pneumoniae and fungi in the case of allergic bronchopulmonary aspergillosis (ABPA), also play a potential role in inducing and exacerbating this disease. Additionally, certain individuals may have a genetic predisposition toward viral induced wheezing and the development of asthma. This paper will discuss host and environmental factors, common pathogens, clinical characteristic, and genetic influences associated with infection related asthma.

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“…During infection, the airway epithelium is a major source of the "alarmin" cytokine interleukin-33 (IL-33). Intriguingly, nasal aspirates from infants with severe RSV disease have elevated levels of IL-33 (7,8), and variants of the IL-33 receptor gene IL1RL1 are associated with severe RSV disease in human infants (9). Immediately following RSV infection in neonatal mice, a robust IL-33 response is elicited in CD45…”

Section: Epithelial Cellsmentioning

confidence: 99%

Crawling with Virus: Translational Insights from a Neonatal Mouse Model on the Pathogenesis of Respiratory Syncytial Virus in Infants

You

Saravia

Siefker

et al. 2016

J Virol

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The infant immune response to respiratory syncytial virus (RSV) remains incompletely understood. Here we review the use of a neonatal mouse model of RSV infection to mimic severe infection in human infants. We describe numerous age-specific responses, organized by cell type, observed in RSV-infected neonatal mice and draw comparisons (when possible) to human infants. R espiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections in infants, and severe RSV disease during infancy is associated with an increased risk of asthma development. The medical and economic burdens of RSV infection are enormous. In the United States alone, there are 85,000 to 144,000 annual hospitalizations with $2.6 billion in associated estimated medical cost (1). Despite its continued impact on global health, RSV remains without a vaccine or adequate therapeutic.While prematurity, immunodeficiency, and congenital heart or chronic lung diseases are risk factors for severe RSV disease, the majority of the infants requiring hospitalization were previously healthy and less than 6 months of age (2), suggesting that age at the time of initial infection is an important predictive factor for disease severity. Therefore, our grasp of severe RSV disease in infants is inevitably tied to our understanding of developmental immunity during the first year of life.The neonatal mouse model of RSV infection has been an invaluable tool for RSV research (3, 4). Briefly, neonatal mice (Յ7 days of age) are infected with RSV and then reinfected 4 weeks later as adults. Compared to mice initially infected as adults, these mice develop the characteristic Th2-biased immunopathologies, including exaggerated pulmonary Th2 cells/cytokines, eosinophilia, mucus hyperproduction, and airway hyperreactivity. In recent years, this model spurred several significant advances in research on how age-dependent differences in various immune and nonimmune cells initiate the immunopathogenesis of RSV infection in infants. This article will briefly discuss said advances, organized by the cell types involved in responding to RSV. EPITHELIAL CELLSThe major cellular target of RSV is airway epithelial cells. In the lower respiratory tract, RSV infects bronchiolar and alveolar (type I and II) epithelial cells (5) and similar cells in mice (6). During infection, the airway epithelium is a major source of the "alarmin" cytokine interleukin-33 (IL-33). Intriguingly, nasal aspirates from infants with severe RSV disease have elevated levels of 8), and variants of the IL-33 receptor gene IL1RL1 are associated with severe RSV disease in human infants (9). Immediately following RSV infection in neonatal mice, a robust IL-33 response is elicited in CD45 Ϫ EpCam ϩ pneumocytes (7); this type of response to RSV infection does not occur in adult mice, suggesting age-dependent regulation of IL-33 expression in the lung. Furthermore, the severity of RSV infection (i.e., Th2-mediated immunopathology) is dependent on the levels of IL-33 early during infection. ILC2SMor...

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IL1RL1 Gene Variants and Nasopharyngeal IL1RL-a Levels Are Associated with Severe RSV Bronchiolitis: A Multicenter Cohort Study

Cited by 37 publications

References 37 publications

Toward Primary Prevention of Asthma. Reviewing the Evidence for Early-Life Respiratory Viral Infections as Modifiable Risk Factors to Prevent Childhood Asthma

Toward Primary Prevention of Asthma. Reviewing the Evidence for Early-Life Respiratory Viral Infections as Modifiable Risk Factors to Prevent Childhood Asthma

Infection-Related Asthma

Crawling with Virus: Translational Insights from a Neonatal Mouse Model on the Pathogenesis of Respiratory Syncytial Virus in Infants

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