Extreme Turnover of CNS Macrophages in Choroid Plexus during Perivascular SIV Infection
Delery EC1, Irons D2, Merino KM1, Sugimoto C1, Cai Y1, Allers C1, MacLean AG1, Kuroda MK1, Kim WK2
1Tulane National Primate Research Center; 2Eastern Virginia Medical School
Increased monocyte turnover and SIV viral load are correlated with an increased prevalence of SIV encephalitis (SIVE) defined by the presence of multinucleated giant cells. Pediatric rhesus macaques have a rapid disease progression characterized by monocyte turnover and elevated plasma viral loads and would therefore be anticipated to have a greater prevalence of SIVE. A retrospective comparison between SIV-infected pediatric macaques, infected adults without encephalitis, and infected adults with encephalitis (SIVE) demonstrated that despite similar plasma viral loads and monocyte turnover rates, infected pediatric macaques exhibited no SIVE. We then sought to elucidate if this difference was due to immunological differences at the choroid plexus, which is a possible mechanism of viral entry into the central nervous system. Using CD163 and CD206 to identify perivascular inflammatory macrophages, MAC387 to identify recently infiltrating myeloid cells, BrdU to identify actively proliferating cells, and DAPI, immunohistochemistry on formalin-fixed paraffin-embedded brain tissue containing choroid plexus was performed. Percent positive cells per nuclei were reported. As expected, uninfected rhesus macaques had the lowest percentage of recently infiltrating monocytes/macrophages (MAC387), with uninfected pediatrics having zero total. Infected pediatrics had the highest percentages of choroid plexus and perivascular macrophages (CD163, CD206), but had the lowest levels of actively proliferating cells (BrdU). Conversely, infected adults had the highest percentage of actively proliferating cells (BrdU) and lower percentages of choroid plexus macrophages (CD163), perivascular macrophages (CD206), & infiltrating monocytes/ macrophages (MAC387). SIVE adults had the second highest percentage of recently infiltrating monocytes/macrophages (MAC387), but still significantly lower than infected pediatrics, which did not have multinucleated giant cells. Interestingly, and contrary to current literature, CD163+ levels in SIVE adults were also much lower than uninfected adults and slightly lower than infected adults without encephalitis. These studies will help elucidate mechanisms of HIV encephalitis.