IRF4-dependent dendritic cells regulate CD8+ T-cell differentiation and memory responses in influenza infection.
Mucosal Immunol
; 12(4): 1025-1037, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-31089186
ABSTRACT
Acute respiratory disease caused by influenza viruses is imperfectly mitigated by annual vaccination to select strains. Development of vaccines that elicit lung-resident memory CD8+ T cells (TRM) would offer more universal protection to seasonal and emerging pandemic viruses. Understanding how lung-resident dendritic cells (DCs) regulate TRM differentiation would be an important step in this process. Here, we used CD11c-cre-Irf4f/f (KO) mice, which lack lung-resident IRF4-dependent CD11b+CD24hi DCs and show IRF4 deficiency in other lung cDC subsets, to determine if IRF4-expressing DCs regulate CD8+ memory precursor cells and TRM during influenza A virus (IAV) infection. KO mice showed defective CD8+ T-cell memory, stemming from a deficit of T regulatory cells and memory precursor cells with decreased Foxo1 expression. Transfer of wild-type CD11b+CD24hi DCs into KO mice restored CD8+ memory precursor cell numbers to wild-type levels. KO mice recovered from a primary infection harbored reduced numbers of CD8+ TRM and showed deficient expansion of IFNγ+CD8+ T cells and increased lung pathology upon challenge with heterosubtypic IAV. Thus, vaccination strategies that harness the function of IRF4-dependent DCs could promote the differentiation of CD8+ TRM during IAV infection.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vírus da Influenza A
/
Células Dendríticas
/
Infecções por Orthomyxoviridae
/
Linfócitos T CD8-Positivos
/
Fatores Reguladores de Interferon
/
Memória Imunológica
Tipo de estudo:
Prognostic_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