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10.1089/aid.2013.0154

http://scihub22266oqcxt.onion/10.1089/aid.2013.0154
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C3976578!3976578!24229417
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suck abstract from ncbi


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pmid24229417      AIDS+Res+Hum+Retroviruses 2014 ; 30 (4): 345-54
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  • Modulation of HIV-1-Induced Activation of Plasmacytoid Dendritic Cells by 6-Desfluoroquinolones #MMPMID24229417
  • Royle CM; Tsai MH; Tabarrini O; Massari S; Graham DR; Aquino VN; Boasso A
  • AIDS Res Hum Retroviruses 2014[Apr]; 30 (4): 345-54 PMID24229417show ga
  • Chronic activation of plasmacytoid dendritic cells (pDCs) is an important contributor to the immunopathogenesis of HIV infection. The quinolone derivative chloroquine (CQ) prevents endosomal acidification, required for toll-like receptor sensing of HIV by pDCs, and is currently under clinical trial as an immunotherapeutic approach. We tested three different 6-desfluoroquinolones (6-DFQs), structurally related to CQ and endowed with antiretroviral activity, for their ability to inhibit HIV-induced pDC activation and interferon (IFN)-? production in peripheral blood mononuclear cells (PBMCs) in vitro. PBMCs from six healthy donors were cultured overnight with aldrithiol-2 (AT-2)-inactivated HIV-1MN in the presence or absence of 6-DFQs or CQ. IFN-? production was measured by ELISA; pDC and monocyte activation was analyzed by flow cytometry. Incubation with HIV labeled with the fluorescent dye DyLight-488 (DL488) was used to test virus uptake by flow cytometry. We found that the 6-DFQs effectively inhibited HIV-induced IFN-? similar to CQ, but only 6-DFQs also inhibited the upregulation of the pDC activation marker CD83. Interestingly, HIV-induced expression of the costimulatory molecule CD80 and, to a lesser extent CD86, was further enhanced on pDCs by 6-DFQs, but not CQ. Conversely, 6-DFQs and CQ had similar inhibitory effects on HIV-induced monocyte activation, consistent with the primary mechanism being associated with IFN-? signaling. Finally, 6-DFQs interfered with HIV interaction with pDCs and monocytes, but not myeloid DCs. Our data indicate that 6-DFQs may interfere with pDC-mediated and IFN-?-dependent immunopathogenesis while supporting pDC differentiation into mature antigen-presenting cells by favoring expression of costimulatory molecules.
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