Cutting edge: independent roles for IRF-3 and IRF-7 in hematopoietic and nonhematopoietic cells during host response to Chikungunya infection.
J Immunol
; 188(7): 2967-71, 2012 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-22371392
ABSTRACT
The host response to Chikungunya virus is dependent on the direct action of type I IFN on infected nonhematopoietic cells. Prior studies have demonstrated that multiple host sensors coordinate an antiviral response; however, the tissue source(s) and signaling pathways for IFN production remain unknown. In this study, we demonstrate that IRF-3 and IRF-7 are functionally redundant, but lack of both factors results in lethal infection in adult mice. Reciprocal bone marrow chimeras indicated that IRF-3 or IRF-7 expression in either hematopoietic or nonhemotopoietic cell compartments was capable of inducing an antiviral response. Interestingly, redundancy of IRF-3 and IRF-7 was age dependent, as neonatal animals lacking either factor succumbed to infection. We further demonstrate that IPS-1 is essential in nonhematopoietic cells and preferentially required during early life. These results highlight the interplay between nonimmune and immune cells during Chikungunya virus infection and suggest an important role for nonhematopoietic cells as a critical source of IFN-α/ß.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
/
Infecções por Alphavirus
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Fator Regulador 3 de Interferon
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Fator Regulador 7 de Interferon
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Fibroblastos
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2012
Tipo de documento:
Article