Recently infiltrating MAC387(+) monocytes/macrophages a third macrophage population involved in SIV and HIV
Caroline Soulas1, Cecily Conerly, Woong-Ki Kim
1Department of Biology, Boston College, Chestnut Hill, Massachusetts, USA.
Abstract:
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.
Insights
Monocyte/macrophage populations in the brain, including recently infiltrated MAC387(+) cells and resident CD68(+) cells, play distinct roles in HIV and SIV encephalitis progression and lesion formation.
Area of Science:
- Neuroimmunology
- Virology
- Cell Biology
Background:
- Monocytes and macrophages are key players in HIV and SIV encephalitis.
- Understanding macrophage heterogeneity is crucial for defining their role in lesion development and viral infection.
Purpose of the Study:
- To define macrophage heterogeneity in SIV encephalitis.
- To elucidate the roles of different macrophage populations in lesion formation and productive infection.
Main Methods:
- In vivo BrdU labeling to track cell proliferation and infiltration.
- Immunohistochemistry using specific markers (CD68, HAM56, CD163, MAC387, SIV-p28) to identify macrophage subtypes and inflammation.
- Quantification of macrophage populations in relation to lesion severity and viral replication.
Main Results:
- Brain lesions comprise resident (CD68(+)HAM56(+)), perivascular (CD163(+)CD68(+)), and infiltrated (MAC387(+)) monocytes/macrophages.
- MAC387(+) cells are recently infiltrated and not productively infected, increasing with mild encephalitis.
- Productive infection and multinucleated giant cells are associated with CD68(+) and CD163(+) macrophages, particularly in severe encephalitis.
Conclusions:
- SIV and HIV encephalitis involve the recruitment of nonproductively infected MAC387(+) monocytes/macrophages and productively infected CD163(+) and CD68(+) macrophages.
- The balance of these populations correlates with encephalitis severity, indicating an active, ongoing inflammatory and infectious process.
- Perivascular and resident macrophages serve as cellular reservoirs for productive viral infection.
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