Proliferation of Perivascular Macrophages Contributes to the Development of Encephalitic Lesions in HIV-Infected Humans and in SIV-Infected Macaques.
The aim of the present study was to investigate if macrophage proliferation occurs in the brain during simian immunodeficiency virus (SIV) infection of adult macaques. We examined the expression of the Ki-67 proliferation marker in the brains of uninfected and SIV-infected macaques with or without encephalitis. Double-label immunohistochemistry using antibodies against the pan-macrophage marker CD68 and Ki-67 showed that there was a significant increase in CD68+Ki-67+ cells in macaques with SIV encephalitis (SIVE) compared to uninfected and SIV-infected animals without encephalitis, a trend that was also confirmed in brain samples from patients with HIV encephalitis. Multi-label immunofluorescence for CD163 and Ki-67 confirmed that the vast majority of Ki-67+ nuclei were localized to CD163+ macrophages in perivascular cuffs and lesions. The proliferative capacity of Ki-67+ perivascular macrophages (PVM) was confirmed by their nuclear incorporation of bromodeoxyuridine. Examining SIVE lesions, using double-label immunofluorescence with antibodies against SIV-Gag-p28 and Ki-67, showed that the population of Ki-67+ cells were productively infected and expanded proportionally with lesions. Altogether, this study shows that there are subpopulations of resident PVM that express Ki-67 and are SIV-infected, suggesting a mechanism of macrophage accumulation in the brain via PVM proliferation.
Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia, United States.
Adam R
AR
Filipowicz
Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia, United States.
Christopher M
CM
McGary
Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia, United States.
Gerard E
GE
Holder
Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia, United States.
Allison A
AA
Lindgren
Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia, United States.
Edward M
EM
Johnson
Division of Immunology, Tulane National Primate Research Center, Covington, Louisiana, United States.
Chie
C
Sugimoto
Division of Immunology, Tulane National Primate Research Center, Covington, Louisiana, United States.
Marcelo J
MJ
Kuroda
Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia, United States.
Woong-Ki
WK
Kim
D000818:Animals; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001808:Blood Vessels / Q000503:physiopathology; D001921:Brain / Q000503:physiopathology; D049109:Cell Proliferation; D004660:Encephalitis / Q000209:etiology* / Q000503:physiopathology; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D019394:Ki-67 Antigen; D008253:Macaca mulatta; D008264:Macrophages / Q000502:physiology*; D008297:Male; D011956:Receptors, Cell Surface; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications*; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D019394:Ki-67 Antigen; D011956:Receptors, Cell Surface