Plasmacytoid Dendritic Cells Suppress HIV-1 Replication but Contribute to HIV-1 Induced Immunopathogenesis in Humanized Mice

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Persistent expression of IFN-I is correlated with disease progression in HIV-1 infected humans or SIV-infected monkeys. Thus, persistent pDC activation has been implicated in contributing to AIDS pathogenesis. To define the role of pDC in HIV-1 infection and immunopathogenesis in vivo, we developed a monoclonal antibody that specifically and efficiently depletes human pDC in all lymphoid organs in humanized mice. We discover that pDC are the critical IFN-I producer cells in response to acute HIV-1 infection, because depletion of pDC completely abolished induction of IFN-I or ISG by HIV-1 infection, correlated with elevated level of HIV-1 replication. When pDC were depleted during chronic HIV-1 infection in humanized mice, pDC were still the major IFN-I producing cells in vivo, which contributed to HIV-1 suppression. Despite of higher level of viral replication in pDC-depleted mice, we found that HIV-induced depletion of human T cells and leukocytes was significantly reduced in lymphoid organs, correlated with reduced cell death induction by HIV-1 infection. Our findings demonstrate that pDC play two opposing roles in HIV-1 pathogenesis: they produce IFN-I to suppress HIV-1 replication and induce death of human immune cells to contribute to HIV-induced T cell depletion and immunopathogenesis.

Vyšlo v časopise: Plasmacytoid Dendritic Cells Suppress HIV-1 Replication but Contribute to HIV-1 Induced Immunopathogenesis in Humanized Mice. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004291
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004291

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