Dendritic Cells Express and Use Multiple HIV Coreceptors
Dendritic cells (DC) are the first immunocompetent cells to encounter antigen at areas of inflammation in mucous membranes1, which are the major sites where the initiation of HIV infection occurs. HIV enters a mucous membrane and interacts with Langerhans cells (LC)/DC resulting in binding of the virus to the cell with or without infection. The cell then migrates and delivers virus to the paracortical region of the draining lymphoid tissue: LC/DC also provide activation stimuli to CD4+ T cells which become infected leading to replication and spread of virus2,3. Recently, in vivo data in the macaque model have clarified certain pathogenic events associated with primary simian immunodeficiency virus (SIV) infection. SIV was placed in the vaginal vault and infected cells were then identified and followed using in situ PCR technology. DC in the lamina propria of the cervicovaginal mucosa were found to contain SIV DNA 2 days after exposure to virus. Infected cells were observed in the sub-capsular and paracortical regions of the draining lymph nodes; this series of events mirrors the course that DCs take upon receiving a signal to migrate from the tissues to lymphoid organs4. Thus, in an animal model of HIV, DC appeared to be responsible for bringing virus from the site of inoculation to the paracortical T cell regions of the draining lymphoid organs leading to viral replication and systemic spread of infection.
KeywordsHuman Immunodeficiency Virus Type Simian Immunodeficiency Virus Stromal Cell Derive Factor Tropic Strain Peripheral Blood Dendritic Cell
Unable to display preview. Download preview PDF.
- 2.Cameron, P. U., I’. S. Freudenthal, J. M. Barker, S. Gezelter, K. Inaba, and R. M. Steinman. 1992. Dendritic cells exposed to human immunodeficiency virus type-1 transmit a vigorous cytopathic infection to CD4’ T cells. Science 257: 383.Google Scholar
- 4.Spira, A. I., P. A. Marx, B. K. Patterson, J. Mahoney, R. A. Koup, S. M. Wolinsky, and D. D. Ho. 1996. Cellular targets of infection and route of viral dissemination after an intravaginal inoculation of simian immunodeficiency virus into rhesus macaques. J Exp Med 183: 215.PubMedCrossRefGoogle Scholar
- 7.Deng, H., R. Liu, W. Ellmeier, S. Choe, D. Unutmaz, M. Burkhart, P. Di Marzio, S. Marmon, R. E. Sutton, C. M. Hill, C. B. Davis, S. C. Peiper, T. J. Schall, D. R. Littman, and N. R. Landau. 1996. Identification of a major co-receptor for primary isolates of HIV-1. Nature 381: 661.PubMedCrossRefGoogle Scholar
- 10.Feng, Y., C. C. Broder, P. E. Kennedy, and E. A. Berger. 1996. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272: 872.Google Scholar
- 12.Sallusto, F., and A. Lanzavecchia. 1994. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med 179: 1109.PubMedCrossRefGoogle Scholar
- 13.Kitaura, M., T. Nakajima, T. Imai, S. Harada, C. Combadiere, H. L. Tiffany, P. M. Murphy, and O. Yoshie. 1996. Molecular cloning of human eotaxin, an eosinophil-selective CC chemokine, and identification of a specific eosinophil eotaxin receptor, CC chemokine receptor 3. J Biol Chem 271: 7725.PubMedCrossRefGoogle Scholar
- 14.Stanley, S., M. A. Ostrowski, J. S. Justement, K. Gantt, S. Hedayati, M. Mannix, K. Roche, D. J. Schwartzentruber, C. H. Fox, and A. S. Fauci. 1996. Effect of immunization with a common recall antigen on viral expression in patients infected with human immunodeficiency virus type 1. N Engl J Med 334: 1222.PubMedCrossRefGoogle Scholar
- 15.Sozzani, S., F. Sallusto, W. Luini, D. Zhou, L. Piemonti, P. Allavena, J. Van Damme, S. Valitutti, A. Lanzavecchia, and A. Mantovani. 1995. Migration of dendritic cells in response to formyl peptides, C5a, and a distinct set of chemokines. J Immunol 155: 3292.Google Scholar