Recently Infiltrating MAC387+ Monocytes/Macrophages

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.

Splenic Damage during SIV Infection

“…Mac387 cells appeared to be a unique population, as they did not express either of the other two macrophage markers, which is consistent with the work of others. 51 Data summarizing the macrophage populations present in the uninfected spleen are listed in Table 3.…”

“…50 These newly infiltrated macrophages have a distinct morphology from resident macrophages and also have different functional capacities. 51,52 The resident and recently infiltrated macrophage subsets may have differing levels of HIV infectivity, and may also promote distinct antiviral and/or inflammatory responses within the spleen. However, the effects of HIV on these different splenic macrophage subsets are not completely understood.…”

Elite Control, Gut CD4 T Cell Sparing, and Enhanced Mucosal T Cell Responses in Macaca nemestrina Infected by a Simian Immunodeficiency Virus Lacking a gp41 Trafficking Motif

“…This finding correlated with the absence of detectable virus in the central nervous system (CNS), where monocyte/mac- rophage trafficking of infected cells is thought to play a critical role in neuro-AIDS (101,102). ⌬GY-infected animals also exhibited a lack of BrdU incorporation in monocytes during chronic infection, which we have shown correlates with macrophage turnover and progression to AIDS (34).…”

“…⌬GY-infected animals also exhibited a lack of BrdU incorporation in monocytes during chronic infection, which we have shown correlates with macrophage turnover and progression to AIDS (34). While there has been recent controversy as to whether myeloid cells isolated from tissues are actually infected or have simply phagocytosed debris from neighboring SIV-infected T cells (103), previous analyses of tissues from SIV-infected macaques (24,35,101,104,105) and the current study show SIV antigens and nucleic acids in tissues from SIVmac239-infected pig-tailed macaques, which were distinguishable from phagocytosed SIV antigens and CD3 ϩ T cell fragments (Fig. 3).…”

Macrophages of genetically characterized familial hypercholesterolaemia patients show up‐regulation of LDL‐receptor‐related proteins

“…Immunohistochemical analysis was performed with the avidin‐biotin immunoperoxidase technique, as previously described 56. Samples were analysed for Apo B (rabbit‐polyclonal anti‐apolipoprotein B; dilution 1:100; Abcam, ab20737, Abcam: Cambridge, UK), LRP5 (rabbit‐polyclonal anti‐LRP5; dilution 1:50; Abcam, ab38311) and MAC387 that is a marker for tissue infiltrating monocytes 57, 58 [anti‐Macrophage antibody (MAC387); dilution 1:100; Abcam, ab22506]. Images were captured and digitized using a Nicon Eclipse 80i microscope and a Retiga 1330i Fast camera.…”