Minocycline Inhibition of Monocyte Activation Correlates with Neuronal Protection in SIV NeuroAIDS

被引:56
作者
Campbell, Jennifer H. [1 ]
Burdo, Tricia H. [1 ]
Autissier, Patrick [1 ]
Bombardier, Jeffrey P. [3 ]
Westmoreland, Susan V. [3 ]
Soulas, Caroline [1 ]
Gonzalez, R. Gilberto [2 ,4 ,5 ]
Ratai, Eva-Maria [2 ,4 ,5 ]
Williams, Kenneth C. [1 ]
机构
[1] Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA
[2] Harvard Univ, Sch Med, Boston, MA USA
[3] New England Reg Primate Res Ctr, Southborough, MA 01772 USA
[4] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA
[5] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA
关键词
SIMIAN IMMUNODEFICIENCY VIRUS; AMYOTROPHIC-LATERAL-SCLEROSIS; PERIVASCULAR MACROPHAGES; NONHUMAN PRIMATE; HIV-INFECTION; CD8(+) LYMPHOCYTES; TYPE-1; INFECTION; T-CELLS; DEMENTIA; DISEASE;
D O I
10.1371/journal.pone.0018688
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: Minocycline is a tetracycline antibiotic that has been proposed as a potential conjunctive therapy for HIV-1 associated cognitive disorders. Precise mechanism(s) of minocycline's functions are not well defined. Methods: Fourteen rhesus macaques were SIV infected and neuronal metabolites measured by proton magnetic resonance spectroscopy ((1)H MRS). Seven received minocycline (4 mg/kg) daily starting at day 28 post-infection (pi). Monocyte expansion and activation were assessed by flow cytometry, cell traffic to lymph nodes, CD16 regulation, viral replication, and cytokine production were studied. Results: Minocycline treatment decreased plasma virus and pro-inflammatory CD14+CD16+ and CD14(lo)CD16+ monocytes, and reduced their expression of CD11b, CD163, CD64, CCR2 and HLA-DR. There was reduced recruitment of monocyte/macrophages and productively infected cells in axillary lymph nodes. There was an inverse correlation between brain NAA/Cr (neuronal injury) and circulating CD14+CD16+ and CD14(lo)CD16+ monocytes. Minocycline treatment in vitro reduced SIV replication CD16 expression on activated CD14+CD16+ monocytes, and IL-6 production by monocytes following LPS stimulation. Conclusion: Neuroprotective effects of minocycline are due in part to reduction of activated monocytes, monocyte traffic. Mechanisms for these effects include CD16 regulation, reduced viral replication, and inhibited immune activation.
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页数:11
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