Efficient infection, activation, and impairment of pDCs in the BM and peripheral lymphoid organs during early HIV-1 infection in humanized rag2â»/â»Î³ Câ»/â» mice in vivo.
Blood
; 117(23): 6184-92, 2011 Jun 09.
Article
en En
| MEDLINE
| ID: mdl-21505190
ABSTRACT
Although plasmacytoid dendritic cells (pDCs) are involved in HIV-1 pathogenesis, the precise mechanism of interaction between pDCs and HIV-1 in vivo is not clear. The conflicting reports in HIV-1-infected patients highlight the importance of studying the interaction between HIV-1 and pDCs in relevant in vivo models. The rag2/γC double knockout (DKO) mouse supports reconstitution of a functional human immune system in central and peripheral lymphoid organs. We report here that functional pDCs were developed in the BM and peripheral lymphoid organs in humanized DKO (DKO-hu) mice. We show that pDCs from both BM and spleen were activated and productively infected during early HIV infection. The activation level of pDCs correlated with that of CD4⺠T-cell activation and apoptosis. Although CD4⺠T cells were preferentially depleted, pDCs were maintained but functionally impaired in the BM and spleen of HIV-infected DKO-hu mice. We conclude that HIV-1 can efficiently infect, activate, and impair pDCs in the BM and spleen, in correlation with CD4⺠T-cell depletion. The humanized mouse will serve as a relevant model to investigate the development and function of pDCs and their role during HIV-1 pathogenesis in vivo.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Médula Ósea
/
Células Dendríticas
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Células de la Médula Ósea
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Infecciones por VIH
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Trasplante de Médula Ósea
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VIH-1
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Modelos Animales de Enfermedad
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Blood
Año:
2011
Tipo del documento:
Article
País de afiliación:
China