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Human Brain Parenchymal Microglia Express CD14 and CD45 and are Productively Infected by HIV‐1 in HIV‐1 Encephalitis
Open accessAbstract
Microglia are endogenous brain macrophages that show distinct phenotypes such as expression of myeloid antigens, ramified morphology, and presence within the neural parenchyma. They play significant roles in a number of human CNS diseases including AIDS dementia. Together with monocytederived (perivascular) macrophages, microglia represent a major target of HIV‐1 infection. However, a recent report challenged this notion based on findings in SIV encephalitis. This study concluded that perivascular macrophages can be distinguished from parenchymal microglial cells by their expression of CD14 and CD45, and that macrophages, but not microglia, are productively infected in SIV and HIV encephalitis. To address whether parenchymal microglia are productively infected in HIV encephalitis, we analyzed expression of CD14, CD45 and HIV‐1 p24 in human brain. Microglia were identified based on their characteristic ramified morphology and location in the neural parenchyma. We found that parenchymal microglia are CD14+ (activated), CD45+ (resting and activated), and constitute approximately two thirds of the p24+ cells in HIV encephalitis cases. These results demonstrate that microglia are major targets of infection by HIV‐1, and delineate possible differences between HIVE and SIVE. Because productively infected tissue macrophages serve as the major viral reservoir, these findings have important implications for AIDS.
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“In cases where the infection was diffuse [23], ramified glial cells had enhanced TSPO positivity, most of which were clearly identifiable as activated microglia.”
From Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain (2009) · cites this paper as [23]
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Cites
CD14, a Receptor for Complexes of Lipopolysaccharide (LPS) and LPS Binding Protein
Wright, S. D., Ramos, R., Tobias, P. S., Ulevitch, R. J., & Mathison, J. C. (1990) · Science · doi:10.1126/science.1698311 · Cited by 3,996
Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain
Lawson, L. J., Perry, V. H., Dri, P., & Gordon, S. (1990) · Neuroscience · doi:10.1016/0306-4522(90)90229-w · Cited by 2,045
The AIDS dementia complex: I. Clinical features
NAVIA, B. A., Jordan, B. D., & Price, R. W. (1986) · Annals of Neurology · doi:10.1002/ana.410190602 · Cited by 1,667
Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo
Hickey, W. F., & Kimura, H. (1988) · Science · doi:10.1126/science.3276004 · Cited by 1,466
Receptor-Dependent Mechanisms of Cell Stimulation by Bacterial Endotoxin
Ulevitch, R. J., & Tobias, P. S. (1995) · Annual Review of Immunology · doi:10.1146/annurev.iy.13.040195.002253 · Cited by 1,442 · cited 1×
“CD14 is the LPS receptor and renders the cells exquisitely sensitive to the actions of LPS, as is the case for microglia (35, 55, 63).”
BackgroundThe AIDS dementia complex: II. Neuropathology
NAVIA, B. A., Cho, E., Petito, C. K., & Price, R. W. (1986) · Annals of Neurology · doi:10.1002/ana.410190603 · Cited by 1,268
Microglia: Intrinsic immuneffector cell of the brain
Gehrmann, J., Matsumoto, Y., & Kreutzberg, G. W. (1995) · Brain Research Reviews · doi:10.1016/0165-0173(94)00015-h · Cited by 1,111
CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia
He, J., Chen, Y., Farzan, M., Choe, H., Öhagen, Å., Gartner, S., Busciglio, J. A., Yang, X., Hofmann, W., Newman, W., et al. (1997) · Nature · doi:10.1038/385645a0 · Cited by 915
Lee, S. C., Liu, W., Dickson, D. W., Brosnan, C., & Berman, J. (1993) · Journal of Immunology · doi:10.4049/jimmunol.150.7.2659 · Cited by 850
Self-citationMacrophages and microglia in the nervous system
Perry, V. H., & Gordon, S. (1988) · Trends in Neurosciences · doi:10.1016/0166-2236(88)90110-5 · Cited by 747
Glass, J. D., Fedor, H. L., Wesselingh, S. L., & McArthur, J. C. (1995) · Annals of Neurology · doi:10.1002/ana.410380510 · Cited by 661
In vivo evolution of HIV-1 co-receptor usage and sensitivity to chemokine-mediated suppression
Scarlatti, G., Tresoldi, E., Björndal, Å. S., Fredriksson, R., Colognesi, C., Deng, H., Malnati, M., Plebani, A., Siccardi, A. G., Littman, D. R., et al. (1997) · Nature Medicine · doi:10.1038/nm1197-1259 · Cited by 631
CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling
Irie-Sasaki, J., Sasaki, T., Matsumoto, W., Opavsky, A., Cheng, M., Welstead, G. G., Griffiths, E. K., Krawczyk, C. M., Richardson, C. D., AITKEN, K. J., et al. (2001) · Nature · doi:10.1038/35053086 · Cited by 572
Ameboid microglia as effectors of inflammation in the central nervous system
Giulian, D. (1987) · Journal of Neuroscience Research · doi:10.1002/jnr.490180123 · Cited by 482
Dementia Associated with the Acquired Immunodeficiency Syndrome
Lipton, S. A., & Gendelman, H. E. (1995) · New England Journal of Medicine · doi:10.1056/nejm199504063321407 · Cited by 468
Sharkey, M. E., Teo, I. A., Greenough, T., Sharova, N., Luzuriaga, K., Sullivan, J. L., Bucy, R. P., Kostrikis, L. G., Haase, A. T., Veryard, C., et al. (2000) · Nature Medicine · doi:10.1038/71569 · Cited by 433
Immunohistochemical identification of HTLV‐III antigen in brains of patients with AIDS
Gabuzda, D. H., Ho, D. D., de la Monte, S. M., Hirsch, M., Rota, T. R., & Sobel, R. A. (1986) · Annals of Neurology · doi:10.1002/ana.410200304 · Cited by 378
Williams, K. C., Corey, S. M., Westmoreland, S. V., Pauley, D. R., Knight, H., deBakker, C. D., Alvarez, X. A., & Lackner, A. A. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.8.905 · Cited by 371
HIV-1 Nef mediates lymphocyte chemotaxis and activation by infected macrophages
Swingler, S., Mann, A. M., Jacqué, J. M., Břicháček, B., Sasseville, V. G., Williams, K., Lackner, A. A., Janoff, E. N., Wang, R., Fisher, D. Z., et al. (1999) · Nature Medicine · doi:10.1038/12433 · Cited by 367
Specific Tropism of HIV-1 for Microglial Cells in Primary Human Brain Cultures
Watkins, B. A., Dorn, H. H., Kelly, W. B., Armstrong, R. C., Potts, A. J., Michaels, F. H., Kufta, C. V., & Dubois-Dalcq, M. E. (1990) · Science · doi:10.1126/science.2200125 · Cited by 340
Geleziunas, R., Xu, W., Takeda, K., Ichijo, H., & Greene, W. C. (2001) · Nature · doi:10.1038/35071111 · Cited by 320
Developmental plasticity of CNS microglia
Santambrogio, L., Belyanskaya, S. L., Fischer, F., Cipriani, B., Brosnan, C. F., Ricciardi‐Castagnoli, P., Stern, L. J., Strominger, J. L., & Riese, R. J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.111152498 · Cited by 309
CD45: new jobs for an old acquaintance
Penninger, J. M., Irie-Sasaki, J., Sasaki, T., & Oliveira-dos-Santos, A. (2001) · Nature Immunology · doi:10.1038/87687 · Cited by 305
Schrager, L. K. (1998) · JAMA · doi:10.1001/jama.280.1.67 · Cited by 301
Albright, A. V., Shieh, J. T. C., Itoh, T., Lee, B., Pleasure, D., O’Connor, M. J., Doms, R. W., & González‐Scarano, F. (1999) · Journal of Virology · doi:10.1128/jvi.73.1.205-213.1999 · Cited by 296
Microglia in human disease, with an emphasis on acquired immune deficiency syndrome.
Dickson, D. W., Mattiace, L. A., Kure, K., Hutchins, K. D., Lyman, W. D., & Brosnan, C. F. (1991) · PubMed · Cited by 275
AIDS dementia complex and HIV‐1 brain infection: Clinical‐virological correlations
Brew, B. J., Rosenblum, M. K., Cronin, K. A., & Price, R. W. (1995) · Annals of Neurology · doi:10.1002/ana.410380404 · Cited by 256
Zink, M. C., Suryanarayana, K., Mankowski, J. L., Shen, A., Piatak, M., Spelman, J. P., Carter, D. L., Adams, R. J., Lifson, J. D., & Clements, J. E. (1999) · Journal of Virology · doi:10.1128/jvi.73.12.10480-10488.1999 · Cited by 223
Rich, E. A., Chen, I. S., Zack, J. A., Leonard, M. L., & O’Brien, W. A. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115559 · Cited by 212
GM‐CSF promotes proliferation of human fetal and adult microglia in primary cultures
Lee, S. C., Liu, W., Brosnan, C. F., & Dickson, D. W. (1994) · Glia · doi:10.1002/glia.440120407 · Cited by 209
Self-citationInfection of brain microglial cells by human immunodeficiency virus type 1 is CD4 dependent
Jordan, C. A., Watkins, B. A., Kufta, C. V., & Dubois-Dalcq, M. E. (1991) · Journal of Virology · doi:10.1128/jvi.65.2.736-742.1991 · Cited by 188
Male Donor-derived Cells in the Brains of Female Sex-mismatched Bone Marrow Transplant Recipients
Unger, E. R., SUNG, J. H., Manivel, J. C., Chenggis, M. L., Blazar, B. R., & Krivit, W. A. (1993) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199309000-00004 · Cited by 187
Kure, K., Lyman, W. D., Weidenheim, K. M., & Dickson, D. W. (1990) · PubMed Central · Cited by 186
Chemokines and HIV replication
Schmidtmayerova, H., Sherry, B. A., & Bukrinsky, M. (1996) · Nature · doi:10.1038/382767a0 · Cited by 178
Popovich, P. G., & Hickey, W. F. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.7.676 · Cited by 154
Lee, S. C., Liu, W., Brosnan, C. F., & Dickson, D. W. (1992) · PubMed · Cited by 149
Self-citationTan, J. R., Town, T., Mori, T., Wu, Y., Saxe, M., Crawford, F., & Mullan, M. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-20-07587.2000 · Cited by 138
The Effects of Human Immunodeficiency Virus in the Central Nervous System
Kolson, D. L., Lavi, E., & González‐Scarano, F. (1998) · Advances in virus research · doi:10.1016/s0065-3527(08)60804-0 · Cited by 137
Pathogenesis of SIV encephalitis. Selection and replication of neurovirulent SIV.
Zink, M. C., Amedee, A. M., Mankowski, J. L., Craig, L. E., Didier, P. J., Carter, D. L., Muñoz, Á., Murphey‐Corb, M., & Clements, J. E. (1997) · Europe PMC (PubMed Central) · Cited by 135
Expression of inducible nitric oxide synthase, interleukin-1 and caspase-1 in HIV-1 encephalitis
Zhao, M., Kim, M.-O., Morgello, S., & Lee, S. C. (2001) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(00)00463-x · Cited by 134
Self-citationUlvestad, E., Williams, K. C., Mørk, S. J., Antel, J. P., & Nyland, H. (1994) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199409000-00008 · Cited by 126
(1994) · PubMed · Cited by 113
Immunoreactivity of CD45, a protein phosphotyrosine phosphatase, in Alzheimer's disease
Masliah, E., Mallory, M., Hansen, L., Alford, M., Albright, T., Terry, R., Shapiro, P., Sundsmo, M., & Saitoh, T. (1991) · Acta Neuropathologica · doi:10.1007/bf00294425 · Cited by 112
Budka, H. (1990) · Acta Neuropathologica · doi:10.1007/bf00294238 · Cited by 96
Liu, W., Brosnan, C. F., Dickson, D. W., & Lee, S. C. (1994) · PubMed Central · Cited by 91
Self-citationCryptococcus neoformans survive and replicate in human microglia.
Lee, S. C., Kress, Y., Zhao, M., Dickson, D. W., & Casadevall, A. (1995) · PubMed · Cited by 91
Self-citationMonocyte CD14: a multifunctional receptor engaged in apoptosis from both sides
Heidenreich, S. (1999) · Journal of Leukocyte Biology · doi:10.1002/jlb.65.6.737 · Cited by 84
The immunology of multiple sclerosis
Ransohoff, R. M., Tuohy, V. K., & Lehmann, P. (1994) · Current Opinion in Neurology · doi:10.1097/00019052-199406000-00011 · Cited by 83
HIV-1 Nef Promotes Survival of Myeloid Cells by a Stat3-dependent Pathway
Briggs, S. D., Scholtz, B., Jacqué, J.-M., Swingler, S., Stevenson, M., & Smithgall, T. E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103244200 · Cited by 78
Unutmaz, D., KewalRamani, V. N., & Littman, D. R. (1998) · Seminars in Immunology · doi:10.1006/smim.1998.0134 · Cited by 74
Productive infection of human fetal microglia by HIV-1.
Lee, S. C., Hatch, W. C., Liu, W., Kress, Y., Lyman, W. D., & Dickson, D. W. (1993) · PubMed Central · Cited by 73
Self-citationHeesen, M. A., Tanabe, S., Berman, M. A., Yoshizawa, I., Luo, Y., Kim, R. J., Post, T. W., Gerard, C. J., & Dorf, M. E. (1996) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19960815)45:4 · Cited by 70
Kitai, R., Zhao, M., Zhang, N., Hua, L. L., & Lee, S. C. (2000) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(00)00315-5 · Cited by 67
Self-citationChemokines and coreceptors in HIV/SIV-host interactions.
Tl, H., & Doms, R. W. (1998) · PubMed · Cited by 67
Serial Passage of Microglial SIV Results in Selection of Homogeneous env Quasispecies in the Brain
Lane, T. E., Buchmeier, M. J., Watry, D. D., Jakubowski, D. B., & Fox, H. S. (1995) · Virology · doi:10.1006/viro.1995.1503 · Cited by 51
Characterization of cultured microglia that can be infected by HIV-1.
Albright, A. V., Shieh, J. T. C., O’Connor, M. J., & González‐Scarano, F. (2000) · PubMed · Cited by 47
Lassmann, H., & Wf, H. (1993) · PubMed · Cited by 43
Microglial tyrosine phosphorylation systems in normal and degenerating brain
Karp, H. L., Tillotson, M. L., Soria, J., Reich, C. A., & Wood, J. G. (1994) · Glia · doi:10.1002/glia.440110310 · Cited by 37
Macrophages and microglia in HIV-related CNS neuropathology.
Dickson, D. W., Lee, S. C., Hatch, W. C., Mattiace, L. A., Brosnan, C. F., & Lyman, W. D. (1994) · PubMed · Cited by 35
Self-citationTarget cells during early SIV encephalopathy
Hurtrel, B., Chakrabarti, L. A., Hurtrel, M., & Montagnier, L. (1993) · Research in Virology · doi:10.1016/s0923-2516(06)80010-5 · Cited by 32
Raghavan, Cheney, Raymond, Joag, Stephens, Adany, Pinsón, Li, Marcario, Jia, et al. (1999) · Neuropathology and Applied Neurobiology · doi:10.1046/j.1365-2990.1999.00185.x · Cited by 31
In Vitro and in Vivo Infection of Rhesus Monkey Microglial Cells by Simian Immunodeficiency Virus
Brinkmann, R., Schwinn, A., Müller, J., Stahl‐Hennig, C., Coulibaly, C., Hunsmann, G., Czub, S., Rethwilm, A., Dörries, R., & ter Meulen, V. (1993) · Virology · doi:10.1006/viro.1993.1407 · Cited by 29
Weidenheim, K. M., Epshteyn, I., & Lyman, W. D. (1993) · PubMed · Cited by 26
Macrophages and T-cell apoptosis in HIV infection: a leading role for accessory cells?
Mahlknecht, U., & Herbein, G. (2001) · Trends in Immunology · doi:10.1016/s1471-4906(01)01898-1 · Cited by 26
Boche, D., Gray, F., Chakrabarti, L. A., Hurtrel, M., Montagnier, L., & Hurtrel, B. (1995) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1995.tb01100.x · Cited by 12
Parchi, P., Giese, A., Capellari, S., Brown, P., Schulz-Schaeffer, W., Windl, O., Zerr, I., Budka, H., Kopp, N., Piccardo, P., et al. (1999) · Annals of Neurology · doi:10.1002/1531-8249(199908)46:2
Research works printed but not linked: 3
- Dickson DW, 1997, Microglia. Textbook of neuropathology, 165
- Dickson DW, 1991, Biology of disease: microglia in human disease, with an emphasis on the aquired immunodeficiency syndrome, Lab Invest, 64, 135
- Lee SC, 1992, Characterization of human fetal dissociated CNS cultures with an emphasis on microglia, Lab Invest, 67, 465
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Metadata
- Authors
- Cosenza;, M. A., Zhao;, M., Si;, Q., & Lee, S. C.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- Lee, Sunhee C.
- Venue
- Brain Pathology
- Publisher
- Wiley
- Published
- 2002-10
- Volume
- 12
- Issue
- 4
- Pages
- 442-455
- ISSN
- 1015-6305 (ISSN-L)
- 1750-3639
- PMC
- PMC8095974
- OpenAlex
- W1990773400
- Cited by
- 238
- References
- 67
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 9 · 2023: 9 · 2022: 10 · 2021: 17 · 2020: 10 · 2019: 13 · 2018: 13 · 2017: 12 · 2016: 8 · 2015: 4 · 2014: 18 · 2013: 18 · 2012: 5
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ai044641-04)
- National Institute of Mental Health (R01MH055477, R24-MH-59724, R24MH059724, MH 55477)
- National Institute of Allergy and Infectious Diseases (AI44641)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Infectious Diseases › Infectious Diseases and Tuberculosis
- Keywords
- microglia, HIV-1 encephalitis, CD14, CD45, perivascular macrophages, SIV encephalitis, HIV-1 p24 antigen, HIV-associated dementia, viral reservoir, brain macrophages
- MeSH terms
- Adult, Antigens, Surface, Brain, Cells, Cultured, Female, Fetus, Humans, Immunohistochemistry, Macrophages, Male, Middle Aged, Monocytes, Biomarkers, HIV-1, AIDS Dementia Complex, HIV Core Protein p24, Leukocyte Common Antigens, Microglia, Lipopolysaccharide Receptors, Cell Size
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