Sex-associated TSLP-induced immune alterations following early-life RSV infection leads to enhanced allergic disease.
Mucosal Immunol
; 12(4): 969-979, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-31076663
ABSTRACT
Many studies have linked severe RSV infection during early-life with an enhanced likelihood of developing childhood asthma, showing a greater susceptibility in boys. Our studies show that early-life RSV infection leads to differential long-term effects based upon the sex of the neonate; leaving male mice prone to exacerbation upon secondary allergen exposure while overall protecting female mice. During initial viral infection, we observed better viral control in the female mice with correlative expression of interferon-ß that was not observed in male mice. Additionally, we observed persistent immune alterations in male mice at 4 weeks post infection. These alterations include Th2 and Th17-skewing, innate cytokine expression (Tslp and Il33), and infiltration of innate immune cells (DC and ILC2). Upon exposure to allergen, beginning at 4 weeks following early-life RSV-infection, male mice show severe allergic exacerbation while female mice appear to be protected. Due to persistent expression of TSLP following early-life RSV infection in male mice, genetically modified TSLPR-/- mice were evaluated and demonstrated an abrogation of allergen exacerbation in male mice. These data indicate that TSLP is involved in the altered immune environment following neonatal RSV-infection that leads to more severe responses in males during allergy exposure, later in life. Thus, TSLP may be a clinically relevant therapeutic target early in life.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Vírus Sinciciais Respiratórios
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Citocinas
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Infecções por Vírus Respiratório Sincicial
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Imunomodulação
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Hipersensibilidade
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Mucosal Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos