| Recently infiltrating MAC387(+) monocytes/macrophages a third macrophage population involved in SIV and HIV encephalitic lesion formation. | |
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MedLine Citation:
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PMID: 21514427 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Monocytes/macrophages are critical components of HIV and SIV encephalitic lesions. We used in vivo BrdU labeling and markers specific to stages of macrophage differentiation or inflammation to define macrophage heterogeneity and to better define the role of macrophage populations in lesion formation and productive infection. Lesions were heterogeneously composed of resident macrophages (CD68(+)HAM56(+)), perivascular macrophages (CD163(+) CD68(+)MAC387(-)), and recently infiltrated MAC387(+) CD68(-)CD163(-) monocytes/macrophages. At 24 and 48 hours after BrdU inoculation, 30% of MAC387(+) monocytes/macrophages were BrdU(+), consistent with their being recently infiltrated. In perivascular cuffs with low-level SIV replication, MAC387(+) monocytes/macrophages outnumbered CD68(+) macrophages. Conversely, lesions with numerous SIV-p28(+) macrophages and multinucleated giant cells had fewer MAC387(+) monocytes/macrophages. The MAC387(+) cells were not productively infected nor did they express detectable CCR2, unlike perivascular macrophages. Overall, we found that the proportion of MAC387(+) cells tends to be higher than the proportion of CD68(+) macrophages in the brain of animals with mild encephalitis; the ratio was reversed with more severe encephalitis. These results suggest that development of SIV and HIV encephalitis is an active and ongoing process that involves the recruitment and accumulation of: i) nonproductively infected MAC387(+) monocytes/macrophages that are present with inflammation (potentially M1-like macrophages), ii) CD163(+) perivascular macrophages (consistent with M2-like macrophages), and iii) CD68(+) or HAM56(+) resident macrophages. The latter two populations are cellular reservoirs for productive infection. |
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Authors:
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Caroline Soulas; Cecily Conerly; Woong-Ki Kim; Tricia H Burdo; Xavier Alvarez; Andrew A Lackner; Kenneth C Williams |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The American journal of pathology Volume: 178 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-04-25 Completed Date: 2011-08-26 Revised Date: 2012-05-01 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 2121-35 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Biology, Boston College, Chestnut Hill, Massachusetts, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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AIDS Dementia Complex
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immunology*,
pathology* Animals Cell Differentiation / physiology Cell Separation Flow Cytometry Fluorescent Antibody Technique Humans Immunohistochemistry In Situ Hybridization Macaca mulatta Macrophages / cytology, immunology*, virology Microscopy, Confocal Monocytes / cytology, immunology, virology Simian Acquired Immunodeficiency Syndrome / immunology*, pathology* Simian immunodeficiency virus |
| Grant Support | |
ID/Acronym/Agency:
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P51RR00164/RR/NCRR NIH HHS; P51RR00168/RR/NCRR NIH HHS; R01NS37654/NS/NINDS NIH HHS; R01NS40237/NS/NINDS NIH HHS; U19MH081835/MH/NIMH NIH HHS |
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