IL-10 and RANTES are Elevated in Nasopharyngeal Secretions of Children with Respiratory Syncytial Virus Infection

Murai, Hiroki; Terada, Akihiko; Mizuno, Mihoko; Asai, Masanori; Hirabayashi, Yu; Shimizu, Seiki; Morishita, Takehiro; Kakita, Hiroki; Hussein, Mohamed Hamed; Ito, Tetsuya; Kato, Ineko; Asai, Kiyofumi; Togari, Hajime

doi:10.2332/allergolint.o-06-454

Cited by 40 publications

(37 citation statements)

References 37 publications

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“…18,19 For example, CCL5 is a key chemokine recruiting Th1 and Th2 proinflammatory cells, and its expression in epithelial cells is induced by the respiratory syncytial virus (RSV). 20,21 This is in line with the evidences that the epithelial barrier in young asthmatics is inherently abnormal 22 and that RSV bronchiolitis is a more important risk factor for the development of asthma and atopy up to the age of 7 years than heredity or environmental factors. 23 Moreover, the candidate genes showing significant association with both the phenotypes, when the case groups were compared with adult controls separately (childhood asthma vs adult control and adult asthma vs adult control), were the same as those observed in the combined analysis (all asthma vs all controls).…”

Section: Discussionsupporting

confidence: 83%

Replication of genetic association studies in asthma and related phenotypes

et al. 2010

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In asthma genetics, the association of highly replicated susceptibility genes lacks consistency across populations. To identify genuine associations, we investigated the reproducibility of the 23 most promising asthma and asthma-related candidate genes in a moderately sized sample from the Japanese population. We compared the frequency of 33 polymorphisms in unrelated cases and controls and tested for their association with asthma, atopy and serum total IgE levels using allele frequency, codominant, dominant and recessive genotype models. On the basis of the consistency of our findings with previous metaanalyses and large replication studies, IL13, TNF, ADAM33, IL4RA and TBXA2R might represent common major asthma and asthma-related trait genes. Individual gene assessment was extended to the interactions between two polymorphisms using our original method. Interactions between TBXA2R and ADAM33, and IL4RA and C3 were suggested to increase the risk for childhood and all asthma (adult and childhood asthma combined). The confirmation of previously reported associations between gene polymorphisms and phenotypes was problematic when as few as several hundred samples per group were used. Stratification of the subjects by environmental factors or other confounding factors may be necessary to improve the sensitivity and reliability of association results. Keywords: association; asthma; atopy; polymorphism; replication INTRODUCTIONAsthma is a heritable trait 1 and investigations to determine the genetic components underlying asthma using linkage mapping and the candidate gene approach have been carried out. By 2006, more than 100 genes were associated with asthma and asthma-related phenotypes; 2 25 of these genes have been replicated in more than six independent association studies. In 2008, this list was complemented with an additional three genes, FLG, NAT2 and CCL15. 3 However, no single polymorphic marker or gene locus has been unanimously labeled as a strong and independent genetic determinant of asthma, and the results for the highly replicated genes have been inconsistent across the tested populations. 3 To identify true associations, it is of critical importance to comprehensively replicate the initial finding. 4 To this aim, we investigated whether the 23 most replicated genes for asthma and asthma-related phenotypes were positively associated with extrinsic childhood and adult asthma, atopy and total serum IgE levels in a moderately sized sample drawn from the Japanese population.We also tested eight genes that were significantly associated with asthma in our subjects: IL13, 5 TBXA2R, 6 GSTP1, 7 ADAM33, 8 MMP9, 9 IL12B, 10 C3 11 and SOCS1. 12 The re-evaluation of these associations is

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Section: Discussionsupporting

confidence: 83%

Replication of genetic association studies in asthma and related phenotypes

et al. 2010

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“…CCL5 and CCL3 are present in peripheral blood and in respiratory secretions at higher concentrations in infants with severe RSV disease (90,95). Additionally, higher concentrations of CCL3 correlate with an increased severity of RSV disease in infants with bronchiolitis (40) and increased symptom scores in adults experimentally infected with RSV (29).…”

Section: Immunopathologymentioning

confidence: 99%

Human Genetic Factors and Respiratory Syncytial Virus Disease Severity

2008

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SUMMARY To explain the wide spectrum of disease severity caused by respiratory syncytial virus (RSV) and because of the limitations of animal models to fully parallel human RSV disease, study of genetic influences on human RSV disease severity has begun. Candidate gene approaches have demonstrated associations of severe RSV in healthy infants with genetic polymorphisms that may alter the innate ability of humans to control RSV (surfactants, Toll-like receptor 4, cell surface adhesion molecules, and others) and those that may control differences in proinflammatory responses or enhanced immunopathology (specific cytokines and their receptors). These studies are reviewed. They are valuable since an understanding of the direction of a polymorphism's effect can help construct a meaningful human RSV disease pathogenesis model. However, the direction, degree, and significance of the statistical association for any given gene are equivocal among studies, and the functional significance of specific polymorphisms is often not even known. Polymorphism frequency distribution differences associated with RSV infection arising from diversity in the genetic background of the population may be confounded further by multiple-hypothesis testing and publication bias, as well as the investigator's perceived importance of a particular pathogenic disease process. Such problems highlight the limitation of the candidate gene approach and the need for an unbiased large-scale genome-wide association study to evaluate this important disease.

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“…S2a; Y32). Thus, IFI35 and CCL5 genes were essentially unresponsive to hRSV infection in the macaque model described herein, despite evidences of their induction in infected airway epithelial cells or patients (Culley et al, 2006;Harrison et al, 1999;Ioannidis et al, 2012;Murai et al, 2007).…”

Section: Expression Of Inflammatory and Ifn-inducible Genes In The Namentioning

confidence: 64%

Evidence for an intranasal immune response to human respiratory syncytial virus infection in cynomolgus macaques

Grandin

Lucas‐Hourani

Clavel³

et al. 2015

Journal of General Virology

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There is no large-scale therapy available against human respiratory syncytial virus (hRSV), a major pathogen responsible for acute respiratory diseases. Macaques represent an interesting animal model to evaluate potential treatments because of their genetic, anatomical and immunological proximity with humans. However, the parameters that influence hRSV growth and control in this model are still poorly understood. We have documented in the following study the influence of age as well as repeated infections on the virological, clinical and immunological parameters of this animal model. Following intranasal inoculation, hRSV replicated in the upper respiratory tract for less than 15 days with no clinical signs regardless of age. Interestingly, we observed the induction of a local immune response at the nasal mucosa as assessed by expression profiles of inflammatory and IFN-stimulated genes. Animals also developed specific antibodies and were immune to reinfection. Thus, we showed that even in infant macaques, intranasal hRSV infection induced both local and systemic immune responses to efficiently control the virus.

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IL-10 and RANTES are Elevated in Nasopharyngeal Secretions of Children with Respiratory Syncytial Virus Infection

Abstract: The increased production of IL-4, IL-10, and RANTES in the airway may play an important role in the pathophysiological mechanisms of RSV infection.

Cited by 40 publications

References 37 publications

Replication of genetic association studies in asthma and related phenotypes

Replication of genetic association studies in asthma and related phenotypes

Human Genetic Factors and Respiratory Syncytial Virus Disease Severity

Evidence for an intranasal immune response to human respiratory syncytial virus infection in cynomolgus macaques

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