Differential Gene Expression of Lymphocytes Stimulated with Rhinovirus A and C in Children with Asthma.
Am J Respir Crit Care Med
; 202(2): 202-209, 2020 07 15.
Article
em En
| MEDLINE
| ID: mdl-32142615
ABSTRACT
Rationale Individuals with asthma have heightened antibody responses to rhinoviruses (RVs), although those specific for RV-C are lower than responses specific for RV-A, suggesting poor immunity to this species.Objectives:
To ascertain and compare T-cell memory responses induced by RV-A and RV-C in children with and without asthma.Methods:
Peripheral blood mononuclear cells from 17 children with asthma and 19 control subjects without asthma were stimulated in vitro with peptide formulations to induce representative species-specific responses to RV-A and RV-C. Molecular profiling (RNA sequencing) was used to identify enriched pathways and upstream regulators.Measurements and MainResults:
Responses to RV-A showed higher expression of IFNG and STAT1 compared with RV-C, and significant expression of CXCL9, 10, and 11 was not found for RV-C. There was no reciprocal increase of T-helper cell type 2 (Th2) cytokine genes or the Th2 chemokine genes CCL11, CCL17, and CCL22. RV-C induced higher expression of CCL24 (eotaxin-2) than RV-A in the responses of children with and without asthma. Upstream regulator analysis showed both RV-A and, although to a lesser extent, RV-C induced predominant Th1 and inflammatory cytokine expression. The responses of children with asthma compared with those without asthma were lower for both RV-A and RV-C while retaining the pattern of gene expression and upstream regulators characteristic of each species. All groups showed activation of the IL-17A pathway.Conclusions:
RV-C induced memory cells with a lower IFN-γ-type response than RV-A without T-helper cell type 2 (Th2) upregulation. Children with asthma had lower recall responses than those without asthma while largely retaining the same gene activation profile for each species. RV-A and RV-C, therefore, induce qualitatively different T-cell responses.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Asma
/
Linfócitos
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Enterovirus
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Infecções por Picornaviridae
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Child
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Child, preschool
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Female
/
Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article