Efficient infection, activation, and impairment of pDCs in the BM and peripheral lymphoid organs during early HIV-1 infection in humanized rag2⁻/⁻γ C⁻/⁻ mice in vivo.

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⁺ T-cell activation and apoptosis. Although CD4⁺ 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⁺ 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.

journal_name

Blood

journal_title

Blood

authors

Zhang L,Jiang Q,Li G,Jeffrey J,Kovalev GI,Su L

doi

10.1182/blood-2011-01-331173

subject

Has Abstract

pub_date

2011-06-09 00:00:00

pages

6184-92

issue

23

eissn

0006-4971

issn

1528-0020

pii

blood-2011-01-331173

journal_volume

117

pub_type

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