Perivascular macrophages in the neonatal macaque brain undergo massive necroptosis after simian immunodeficiency virus infection.

Autor:	Bohannon DG; Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA., Wang Y; Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA., Reinhart CH; Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA., Hattler JB; Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA., Luo J; EVMS-Sentara Healthcare Analytics and Delivery Science Institute, Eastern Virginia Medical School, Norfolk, VA., Okhravi HR; Glennan Center for Geriatrics and Gerontology, Eastern Virginia Medical School, Norfolk, VA., Zhang J; Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE., Li Q; Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE., Kuroda MJ; Center for Comparative Medicine, University of California, Davis, Davis, CA., Kim J; Cedars-Sinai Medical Center, University of California, Los Angeles, Los Angeles, CA., Kim WK; Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA.
Jazyk:	angličtina
Zdroj:	Brain pathology (Zurich, Switzerland) [Brain Pathol] 2020 May; Vol. 30 (3), pp. 603-613. Date of Electronic Publication: 2019 Dec 26.
DOI:	10.1111/bpa.12808
Abstrakt:	We previously showed that rhesus macaques neonatally infected with simian immunodeficiency virus (SIV) do not develop SIV encephalitis (SIVE) and maintain low brain viral loads despite having similar plasma viral loads compared to SIV-infected adults. We hypothesize that differences in myeloid cell populations that are the known target of SIV and HIV in the brain contribute to the lack of neonatal susceptibility to lentivirus-induced encephalitis. Using immunohistochemistry and immunofluorescence microscopy, we examined the frontal cortices from uninfected and SIV-infected infant and adult macaques (n = 8/ea) as well as adults with SIVE (n = 4) to determine differences in myeloid cell populations. The number of CD206+ brain perivascular macrophages (PVMs) was significantly greater in uninfected infants than in uninfected adults and was markedly lower in SIV-infected infants while microglia numbers were unchanged across groups. CD206+ PVMs, which proliferate after infection in SIV-infected adults, did not undergo proliferation in infants. While virtually all CD206+ cells in adults are also CD163+, infants have a distinct CD206 single-positive population in addition to the double-positive population commonly seen in adults. Notably, we found that more than 60% of these unique CD206+CD163- PVMs in SIV-infected infants were positive for cleaved caspase-3, an indicator of apoptosis, and that nearly 100% of this subset were concomitantly positive for the necroptosis marker receptor-interacting protein kinase-3 (RIP3). These findings show that distinct subpopulations of PVMs found in infants undergo programmed cell death instead of proliferation following SIV infection, which may lead to the absence of PVM-dependent SIVE and the limited size of the virus reservoir in the infant brain. (© 2019 International Society of Neuropathology.)
Databáze:	MEDLINE
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