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Cellular and humoral immunity of virus-induced asthma.

Okayama Y - Front Microbiol (2013)

Bottom Line: Severe RSV- and HRV-induced bronchiolitis may be associated with a deficiency in the innate immune response to RSV and HRV.Administration of Palivizumab, a humanized monoclonal antibody that targets the A antigenic site of the Fusion-protein of RSV, decreases the risk of hospitalization in high-risk infants and the risk of recurrent of wheezing.However, palivizumab did not have any effect on subsequent recurrent wheezing in children with a family history of atopy.

View Article: PubMed Central - PubMed

Affiliation: Allergy and Immunology Group, Research Institute of Medical Science, Nihon University School of Medicine Tokyo, Japan.

ABSTRACT
Asthma inception is associated with respiratory viral infection, especially infection with respiratory syncytial virus (RSV) and/or human rhinovirus (HRV), in the vast majority of cases. However, the reason why RSV and HRV induce the majority of bronchiolitis cases during early childhood and why only a small percentage of children with RSV- and HRV-induced bronchiolitis later develop asthma remains unclear. A genetic association study has revealed the important interaction between viral illness and genetic variants in patients with asthma. Severe RSV- and HRV-induced bronchiolitis may be associated with a deficiency in the innate immune response to RSV and HRV. RSV and HRV infections in infants with deficient innate immune response and the dysfunction of regulatory T cells are considered to be a risk factor for the development of asthma. Sensitization to aeroallergens, beginning in the first year of life, consistently predisposes children to HRV-induced wheezing illnesses, but the converse is not true. Some evidence of virus specificity exists, in that allergic sensitization specifically increased the risk of wheezing in individuals infected with HRV, but not RSV. Administration of Palivizumab, a humanized monoclonal antibody that targets the A antigenic site of the Fusion-protein of RSV, decreases the risk of hospitalization in high-risk infants and the risk of recurrent of wheezing. However, palivizumab did not have any effect on subsequent recurrent wheezing in children with a family history of atopy. These findings suggest that infection with RSV and infection with HRV might predispose individuals to recurrent wheezing through an atopy-independent and an atopy-dependent mechanism, respectively. Respiratory virus-induced wheezing illnesses may encompass multiple sub-phenotypes that relate to asthma in different ways.

No MeSH data available.


Related in: MedlinePlus

Possible immunological mechanisms of HRV -induced bronchial asthma in infants. Sensitization to aeroallergens, beginning in the first year of life, consistently predisposes children to HRV-induced wheezing illnesses. Ongoing allergic inflammation in the airways may directly lead to impairment of the epithelial cell barrier and antiviral response. Following aggregation of Fcε RI, HRV-induced IFN-α and IFN-λ1 production from PBMCs and DCs is significantly reduced compared to that by HRV stimulation alone. Furthermore, impairment of virus-induced IFNs from epithelial cells due to genetic variants increases virus replication. HRV infection upregulates TSLP production in epithelial cells (Kato et al., 2007). Neonatal lung DCs express higher baseline levels of OX40 ligand (OX40L) and lower cytoplasmic levels of IL-12 than lung DCs from adult lung DCs. TSLP upregulates the expression of OX40L on DCs. Airway inflammation and AHR may be enhanced after re-infection
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Figure 1: Possible immunological mechanisms of HRV -induced bronchial asthma in infants. Sensitization to aeroallergens, beginning in the first year of life, consistently predisposes children to HRV-induced wheezing illnesses. Ongoing allergic inflammation in the airways may directly lead to impairment of the epithelial cell barrier and antiviral response. Following aggregation of Fcε RI, HRV-induced IFN-α and IFN-λ1 production from PBMCs and DCs is significantly reduced compared to that by HRV stimulation alone. Furthermore, impairment of virus-induced IFNs from epithelial cells due to genetic variants increases virus replication. HRV infection upregulates TSLP production in epithelial cells (Kato et al., 2007). Neonatal lung DCs express higher baseline levels of OX40 ligand (OX40L) and lower cytoplasmic levels of IL-12 than lung DCs from adult lung DCs. TSLP upregulates the expression of OX40L on DCs. Airway inflammation and AHR may be enhanced after re-infection

Mentions: A prospective, repeated characterization of a birth cohort demonstrated that sensitization to aeroallergens, beginning in the first year of life, consistently predisposes children to viral wheezing illnesses and that the converse is not true (Jackson et al., 2013; Figure 1). Some evidence suggests virus specificity, in that allergic sensitization specifically increased the risk of wheezing in individuals with HRV infections, but not those with RSV infections. This sequential relationship and the plausible mechanisms by which allergic sensitization can lead to severer HRV-induced lower respiratory illnesses support a causal role for allergic sensitization in this developmental pathway (Jackson et al., 2013). Subrata et al. (2009) suggested that interactions between innate antiviral and allergic inflammatory pathways may lead to severer viral illnesses in atopic children. Ongoing allergic inflammation in the airways may directly lead to impairment of the epithelial cell barrier and the antiviral response (Figure 1). Accordingly, respiratory viral infection in atopic children may initiate an atopy-dependent cascade that amplifies and sustains airway inflammation initiated by innate antiviral immunity via harnessing the underlying atopy-associated mechanisms (Subrata et al., 2009). Allergic asthmatic children had higher surface expression of FcεRIα on plasmacytoid (p) DCs and myeloid (m) DCs when compared with that seen in nonallergic, nonasthmatic children. The percentage of FcεRIα + pDCs and mDCs in allergic asthmatic children was inversely correlated with HRV-induced IFN-α and IFN-λ1, and IFN-α production levels, respectively (Figure 1). Following aggregation of Fcε RI, HRV-induced IFN-α and IFN-λ1 production from peripheral blood mononuclear cells (PBMCs) was significantly reduced compared to that by HRV stimulation alone (Durrani et al., 2012). These effects may explain why children with allergic asthma have more frequent and severe HRV-induced wheezing and asthma exacerbations. In contrast, the administration of palivizumab prophylaxis had no effect on subsequent recurrent wheezing in children with a family history of atopy (Simoes et al., 2010). This finding suggests that RSV infection predisposes individuals to recurrent wheezing through an atopy-independent mechanism. Several asthmatic or wheezing phenotypes exist in children (Fitzpatrick et al., 2011). Therefore, respiratory virus-induced wheezing illnesses can encompass multiple sub-phenotypes that relate to asthma in different ways.


Cellular and humoral immunity of virus-induced asthma.

Okayama Y - Front Microbiol (2013)

Possible immunological mechanisms of HRV -induced bronchial asthma in infants. Sensitization to aeroallergens, beginning in the first year of life, consistently predisposes children to HRV-induced wheezing illnesses. Ongoing allergic inflammation in the airways may directly lead to impairment of the epithelial cell barrier and antiviral response. Following aggregation of Fcε RI, HRV-induced IFN-α and IFN-λ1 production from PBMCs and DCs is significantly reduced compared to that by HRV stimulation alone. Furthermore, impairment of virus-induced IFNs from epithelial cells due to genetic variants increases virus replication. HRV infection upregulates TSLP production in epithelial cells (Kato et al., 2007). Neonatal lung DCs express higher baseline levels of OX40 ligand (OX40L) and lower cytoplasmic levels of IL-12 than lung DCs from adult lung DCs. TSLP upregulates the expression of OX40L on DCs. Airway inflammation and AHR may be enhanced after re-infection
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3753555&req=5

Figure 1: Possible immunological mechanisms of HRV -induced bronchial asthma in infants. Sensitization to aeroallergens, beginning in the first year of life, consistently predisposes children to HRV-induced wheezing illnesses. Ongoing allergic inflammation in the airways may directly lead to impairment of the epithelial cell barrier and antiviral response. Following aggregation of Fcε RI, HRV-induced IFN-α and IFN-λ1 production from PBMCs and DCs is significantly reduced compared to that by HRV stimulation alone. Furthermore, impairment of virus-induced IFNs from epithelial cells due to genetic variants increases virus replication. HRV infection upregulates TSLP production in epithelial cells (Kato et al., 2007). Neonatal lung DCs express higher baseline levels of OX40 ligand (OX40L) and lower cytoplasmic levels of IL-12 than lung DCs from adult lung DCs. TSLP upregulates the expression of OX40L on DCs. Airway inflammation and AHR may be enhanced after re-infection
Mentions: A prospective, repeated characterization of a birth cohort demonstrated that sensitization to aeroallergens, beginning in the first year of life, consistently predisposes children to viral wheezing illnesses and that the converse is not true (Jackson et al., 2013; Figure 1). Some evidence suggests virus specificity, in that allergic sensitization specifically increased the risk of wheezing in individuals with HRV infections, but not those with RSV infections. This sequential relationship and the plausible mechanisms by which allergic sensitization can lead to severer HRV-induced lower respiratory illnesses support a causal role for allergic sensitization in this developmental pathway (Jackson et al., 2013). Subrata et al. (2009) suggested that interactions between innate antiviral and allergic inflammatory pathways may lead to severer viral illnesses in atopic children. Ongoing allergic inflammation in the airways may directly lead to impairment of the epithelial cell barrier and the antiviral response (Figure 1). Accordingly, respiratory viral infection in atopic children may initiate an atopy-dependent cascade that amplifies and sustains airway inflammation initiated by innate antiviral immunity via harnessing the underlying atopy-associated mechanisms (Subrata et al., 2009). Allergic asthmatic children had higher surface expression of FcεRIα on plasmacytoid (p) DCs and myeloid (m) DCs when compared with that seen in nonallergic, nonasthmatic children. The percentage of FcεRIα + pDCs and mDCs in allergic asthmatic children was inversely correlated with HRV-induced IFN-α and IFN-λ1, and IFN-α production levels, respectively (Figure 1). Following aggregation of Fcε RI, HRV-induced IFN-α and IFN-λ1 production from peripheral blood mononuclear cells (PBMCs) was significantly reduced compared to that by HRV stimulation alone (Durrani et al., 2012). These effects may explain why children with allergic asthma have more frequent and severe HRV-induced wheezing and asthma exacerbations. In contrast, the administration of palivizumab prophylaxis had no effect on subsequent recurrent wheezing in children with a family history of atopy (Simoes et al., 2010). This finding suggests that RSV infection predisposes individuals to recurrent wheezing through an atopy-independent mechanism. Several asthmatic or wheezing phenotypes exist in children (Fitzpatrick et al., 2011). Therefore, respiratory virus-induced wheezing illnesses can encompass multiple sub-phenotypes that relate to asthma in different ways.

Bottom Line: Severe RSV- and HRV-induced bronchiolitis may be associated with a deficiency in the innate immune response to RSV and HRV.Administration of Palivizumab, a humanized monoclonal antibody that targets the A antigenic site of the Fusion-protein of RSV, decreases the risk of hospitalization in high-risk infants and the risk of recurrent of wheezing.However, palivizumab did not have any effect on subsequent recurrent wheezing in children with a family history of atopy.

View Article: PubMed Central - PubMed

Affiliation: Allergy and Immunology Group, Research Institute of Medical Science, Nihon University School of Medicine Tokyo, Japan.

ABSTRACT
Asthma inception is associated with respiratory viral infection, especially infection with respiratory syncytial virus (RSV) and/or human rhinovirus (HRV), in the vast majority of cases. However, the reason why RSV and HRV induce the majority of bronchiolitis cases during early childhood and why only a small percentage of children with RSV- and HRV-induced bronchiolitis later develop asthma remains unclear. A genetic association study has revealed the important interaction between viral illness and genetic variants in patients with asthma. Severe RSV- and HRV-induced bronchiolitis may be associated with a deficiency in the innate immune response to RSV and HRV. RSV and HRV infections in infants with deficient innate immune response and the dysfunction of regulatory T cells are considered to be a risk factor for the development of asthma. Sensitization to aeroallergens, beginning in the first year of life, consistently predisposes children to HRV-induced wheezing illnesses, but the converse is not true. Some evidence of virus specificity exists, in that allergic sensitization specifically increased the risk of wheezing in individuals infected with HRV, but not RSV. Administration of Palivizumab, a humanized monoclonal antibody that targets the A antigenic site of the Fusion-protein of RSV, decreases the risk of hospitalization in high-risk infants and the risk of recurrent of wheezing. However, palivizumab did not have any effect on subsequent recurrent wheezing in children with a family history of atopy. These findings suggest that infection with RSV and infection with HRV might predispose individuals to recurrent wheezing through an atopy-independent and an atopy-dependent mechanism, respectively. Respiratory virus-induced wheezing illnesses may encompass multiple sub-phenotypes that relate to asthma in different ways.

No MeSH data available.


Related in: MedlinePlus