Genetic Susceptibility to Respiratory Syncytial Virus Bronchiolitis in Preterm Children Is Associated With Airway Remodeling Genes and Innate Immune Genes

Siezen, Christine L. E.; Bont, Louis; Hodemaekers, Hennie M.; Ermers, Marieke J. J.; Doornbos, Gerda; Slot, Ruben vanʼt; Wijmenga, Cisca; Houwelingen, Hans C. van; Kimpen, Jan L. L.; Kimman, Tjeerd G.; Hoebee, Barbara; Janssen, Riny

doi:10.1097/inf.0b013e31818e2aa9

Cited by 66 publications

(48 citation statements)

References 14 publications

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“…Interferons (IFNs), produced in innate and adaptive immunity, can affect many cellular functions. Upon RSV infection, epithelial cells and infiltrating leukocytes produce type I IFNs (IFN-a/b) against the viral replication and development of disease [7]. Janssen et al [8] performed a large scale genetic association study in which they determined 347 single nucleotide polymorphisms (SNPs) in 470 children hospitalized for RSV bronchiolitis, their parents, and 1008 population controls using a candidate gene approach.…”

Section: Genetic Polymorphisms Of Cytokinesmentioning

confidence: 99%

“…The result indicated that the SNP IFNA5 (rs10757212) demonstrated the strongest association with susceptibility to RSV bronchiolitis in children. Their current study suggested that two SNPs of IFNA13 (rs643070, c.À603G>A) and IFNAR2 (rs7279064, Phe 10 Val) only have an effect in children born at term and not in preterm children, born with underdeveloped lungs [7]. IFN-c, the only type II IFN, is an important Th1 cytokine.…”

Section: Genetic Polymorphisms Of Cytokinesmentioning

confidence: 99%

See 1 more Smart Citation

The role of cytokines and chemokines in severe respiratory syncytial virus infection and subsequent asthma

Zeng

et al. 2011

Cytokine

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Section: Genetic Polymorphisms Of Cytokinesmentioning

confidence: 99%

Section: Genetic Polymorphisms Of Cytokinesmentioning

confidence: 99%

The role of cytokines and chemokines in severe respiratory syncytial virus infection and subsequent asthma

Zeng

et al. 2011

Cytokine

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“…These data suggest that overexpression of TGF-␤ or IL-17 may promote infiltration of neutrophils, which may be involved in the development of severe RSV airway disease. Furthermore, an SNP in the receptor for TGF-␤ was found to be protective against severe RSV infection in preterm infants (55).…”

Section: Discussionmentioning

confidence: 99%

Transforming Growth Factor Beta Is a Major Regulator of Human Neonatal Immune Responses following Respiratory Syncytial Virus Infection

Thornburg

Shepherd

Crowe

2010

J Virol

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Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality. Previous studies have suggested that T-cell responses may contribute to RSV immunopathology, which could be driven by dendritic cells (DCs). DCs are productively infected by RSV, and during RSV infections, there is an increase of DCs in the lungs with a decrease in the blood. Pediatric populations are particularly susceptible to severe RSV infections; however, DC responses to RSV from pediatric populations have not been examined. In this study, primary isolated DCs from cord blood and adult peripheral blood were compared after RSV infection. Transcriptional profiling and biological network analysis identified transforming growth factor beta (TGF-␤) and associated signaling molecules as differentially regulated in the two age groups. TGF-␤1 was decreased in RSV-infected adult-blood DCs but increased in RSV-infected cord blood DCs. Coculture of adult RSV-infected DCs with autologous T cells induced secretion of gamma interferon (IFN-␥), interleukin 12p70 (IL-12p70), IL-2, and tumor necrosis factor alpha (TNF-␣). Conversely, coculture of cord RSV-infected DCs and autologous T cells induced secretion of IL-4, IL-6, IL-1␤, and IL-17. Addition of purified TGF-␤1 to adult DC-T-cell cocultures reduced secretion of IFN-␥, IL-12p70, IL-2, and TNF-␣, while addition of a TGF-␤ chemical inhibitor to cord DC-T-cell cocultures increased secretion of IL-12p70. These data suggest that TGF-␤ acts as a major regulator of RSV DC-T-cell responses, which could contribute to immunopathology during infancy.Human respiratory syncytial virus (RSV), an enveloped negative-strand RNA virus in the family Paramyxoviridae, is the most common viral cause of severe bronchiolitis and pneumonia in infants and young children (10). RSV mainly infects cells of the nasopharynx and lung but can also be detected in circulating blood mononuclear cells (16). Both adaptive and innate responses play a role in protecting hosts from RSV disease. Antibodies do not appear to play a major role in controlling primary infection (25). However, studies using depletion of B lymphocytes indicate that antibodies are necessary for preventing reinfection, and the level of passively acquired anti-RSV maternal antibodies appears to correlate with de-

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“…This included the transcriptional regulator Jun, alpha interferon (IFN-α), nitric oxide synthase, and the vitamin D receptor. The more recent study of preterm children by the same group [14] also indicated a critical association with innate immune system genes and bronchiolitis susceptibility.…”

Section: Spread Of Infectionmentioning

confidence: 91%

Variability of Respiratory Syncytial Virus Seasonality and Mortality

Light¹

2012

Respiratory Diseases

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Genetic Susceptibility to Respiratory Syncytial Virus Bronchiolitis in Preterm Children Is Associated With Airway Remodeling Genes and Innate Immune Genes

Cited by 66 publications

References 14 publications

The role of cytokines and chemokines in severe respiratory syncytial virus infection and subsequent asthma

The role of cytokines and chemokines in severe respiratory syncytial virus infection and subsequent asthma

Transforming Growth Factor Beta Is a Major Regulator of Human Neonatal Immune Responses following Respiratory Syncytial Virus Infection

Variability of Respiratory Syncytial Virus Seasonality and Mortality

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