Dendritic Cell-Specific Intercellular Adhesion Molecule 3-Grabbing Nonintegrin/CD209 Is Abundant on Macrophages in the Normal Human Lymph Node and Is Not Required for Dendritic Cell Stimulation of the Mixed Leukocyte Reaction
Open accessAbstract
The C-type lectin dendritic cell-specific ICAM 3-grabbing nonintegrin (DC-SIGN)/CD209 efficiently binds several pathogens, including HIV-1. DC-SIGN is expressed on monocyte-derived DCs in culture, and importantly, it is able to sequester HIV-1 within cells and facilitate transmission of virus to CD4+ T cells. To investigate DC-SIGN function, we have generated new mAbs. We report in this study that these and prior anti-DC-SIGN mAbs primarily label macrophages in the medullary sinuses of noninflamed human lymph node. In contrast, expression is not detected on most DCs in the T cell area, except for occasional cells. We also noted that IL-4 alone can induce expression of DC-SIGN in CD14+ monocytes and circulating blood DCs. However, blockade of DC-SIGN with Abs and DC-SIGN small interfering RNA did not result in a major reduction in the capacity of these DCs to transfer HIV to T cells, confirming significant DC-SIGN-independent mechanisms. The blocking approaches did reduce HIV-1 transmission by DC-SIGN-transfected cells by >90%. DC-SIGN blockade also did not reduce the ability of DCs to stimulate T cell proliferation in the MLR. These results indicate that DC-SIGN has the potential to contribute to macrophage function in normal human lymph node, and that DCs do not require DC-SIGN to transmit HIV or to initiate T cell responses.
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There exists a DC-SIGN-independent mechanism of trans-infection with HIV-1 viral particles.
“However, the results of other studies indicate the existence of a DC-SIGN-independent mechanism of trans-infection with HIV-1 viral particles [81,82,83,84].”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [83]
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“HIV from MDDC to T cells (18, 19), DC-SIGN may be involved”
BackgroundDermal-Type Macrophages Expressing CD209/DC-SIGN Show Inherent Resistance to Dengue Virus Growth
Kwan, W.-H., Navarro-Sánchez, E., Dumortier, H., Decossas, M., Vachon, H., dos Santos, F. D., Fridman, H., Rey, F., Harris, E., Desprès, P., et al. (2008) · PLoS Neglected Tropical Diseases · doi:10.1371/journal.pntd.0000311 · Cited by 57
“Western blotting of cell lysates confirmed the presence of CD209 as a major band of 49 kDa in both cell-types [13] (Figure S1B).”
BackgroundThe pro and anti-inflammatory activities of immunoglobulin G
Lux, A., Aschermann, S., Biburger, M., & Nimmerjahn, F. (2009) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2009.117101 · Cited by 52 · see citing works
LILRA2 Activation Inhibits Dendritic Cell Differentiation and Antigen Presentation to T Cells
Lee, D. J., Sieling, P. A., Ochoa, M. T., Krutzik, S. R., Guo, B., Hernandez, M., Rea, T. H., Cheng, G., Colonna, M., & Modlin, R. L. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.12.8128 · Cited by 53 · see citing works
“activated tonsil (30), lymph node (31), and rheumatoid arthritis”
BackgroundFunctional comparison of mouse CIRE/mouse DC-SIGN and human DC-SIGN
Caminschi, I., Corbett, A., Zahra, C., Lahoud, M., Lucas, K., Sofi, M., Vremec, D., Gramberg, T., Pöhlmann, S., Curtis, J., et al. (2006) · International Immunology · doi:10.1093/intimm/dxl011 · Cited by 54
“(57) .”
BackgroundDendritic Cells From the Cervical Mucosa Capture and Transfer HIV-1 via Siglec-1
Perez-Zsolt, D., Cantero-Pérez, J., Erkizia, I., Benet, S., Pino, M., Serra-Peinado, C., Hernández-Gallego, A., Castellví, J., Tapia, G., Arnau-Saz, V., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00825 · Cited by 52 · see citing works
“Alternatively, supernatants from these co-cultures were transferred to 0.2× 106 DCs to assess Siglec-1 induction 24 h later with a FACSCalibur, labeling cells with a mAb anti-Siglec-1-PE or a matched isotypePE control (both from AbD Serotec).”
MethodInfluentialHIV-1 Trans Infection of CD4 + T Cells by Professional Antigen Presenting Cells
Rinaldo, C. R. (2013) · Scientifica · doi:10.1155/2013/164203 · Cited by 46 · see citing works
Antigen structure affects cellular routing through DC-SIGN
Jarvis, C. M., Zwick, D. B., Grim, J. C., Alam, M. M., Prost, L. R., Gardiner, J. C., Park, S., Zimdars, L. L., Sherer, N. M., & Kiessling, L. L. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1820165116 · Cited by 59 · see citing works
“Consistent with these data, prior studies have shown that HIV internalization and transmission is inhibited by α-DC-SIGN blocking antibodies in Raji/DCSIGN cells but not in DCs, implicating that other lectins are capable of facilitating viral uptake in when DC-SIGN is unavailable (50, 51).”
ResultBozzacco, L., Trumpfheller, C., Huang, Y.-X., Longhi, M. P., Shimeliovich, I., Schauer, J. D., Park, C. G., & Steinman, R. (2009) · European Journal of Immunology · doi:10.1002/eji.200939748 · Cited by 50
Self-citationImmune recruitment or suppression by glycan engineering of endogenous and therapeutic antibodies
Le, N. P. L., Bowden, T. A., Struwe, W. B., & Crispin, M. (2016) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2016.04.016 · Cited by 49 · see citing works
“phages [254,255], murine SIGN-R1 is not expressed on such cell types.”
BackgroundDuvall, M. G., Loré, K., Blaak, H., Ambrozak, D. R., Adams, W. C. T., Santos, K., Geldmacher, C., Mascola, J. R., McMichael, A. J., Jaye, A., et al. (2007) · Journal of Virology · doi:10.1128/jvi.00976-07 · Cited by 45 · see citing works
“, by becoming productively infected and passing virus to T cells (11, 35, 38, 47, 66), by transmitting virus through an infectious synapse of DCs and T cells (1, 45), or by capturing virions in the absence of productive infection and transferring the virus to CD4 T cells in trans (3, 26, 27, 29, 30, 65, 68, 70, 71).”
BackgroundAlzogaray, V., Danquah, W., Aguirre, A., Urrutia, M., Berguer, P. M., Véscovi, E. G., Haag, F., Koch‐Nolte, F., & Goldbaum, F. A. (2010) · The FASEB Journal · doi:10.1096/fj.10-162958 · Cited by 41 · see citing works
“With respect to macrophages and other antigen-presenting cells, targeted delivery of SpvB-neutralizing VHHs to the endosomal compart- ment of macrophages might also be achieved by genetic fusion of the nanobody to an antibody specific for an endocytosis receptor such as CD209/DCSIGN (60).”
Domínguez-Soto, A., Aragoneses‐Fenoll, L., Gómez-Aguado, F., Corcuera, M., Clària, J., García-Monzón, C., Bustos, M., & Corbí, Á. (2008) · Hepatology · doi:10.1002/hep.22678 · Cited by 47 · see citing works
“7, 8 DC-SIGN is expressed on myeloid dendritic cells (DCs), 1, 9 alternatively activated in vitro macrophages, 10 interstitial DCs, 11 a subset of CD14ϩ peripheral blood DCs, 12 and macrophages from various tissues, [13] [14] [15] whereas L-SIGN is exclusively expressed on endothelial cells of the liver, lymph nodes,…”
BackgroundIdentification of the Optimal DC-SIGN Binding Site on Human Immunodeficiency Virus Type 1 gp120
Hong, P., Nguyen, S., Young, S., Su, S. V., & Lee, B. (2007) · Journal of Virology · doi:10.1128/jvi.01765-06 · Cited by 47 · see citing works
“While the cis enhancement effect of DC-SIGN appears to be real (11, 28), the trans enhancement effect of DC-SIGN remains controversial, especially with regard to its role in DCmediated viral transfer to T cells (2, 11, 14, 21, 36, 58, 59).”
BackgroundDC-SIGN–LEF1/TCF1–miR-185 feedback loop promotes colorectal cancer invasion and metastasis
Yuan, M.-L., Zhang, X.-S., Zhang, J., Wang, K., Zhang, Y., Shang, W., Zhang, Y.-N., Cui, J.-Y., Shi, X., Na, H., et al. (2019) · Cell Death and Differentiation · doi:10.1038/s41418-019-0361-2 · Cited by 45 · see citing works
Dettogni, R. S., Tristão-Sá, R., dos Santos, M. D., da Silva, F. F., & Louro, I. (2015) · Human Immunology · doi:10.1016/j.humimm.2015.09.026 · Cited by 45
Cao, J., Jin, Y., Li, W., Zhang, B., He, Y., Liu, H., Xia, N.-S., Wei, H., & Yan, J. (2013) · BMC Immunology · doi:10.1186/1471-2172-14-39 · Cited by 45
“tissues [45], and this give perspective for its application”
BackgroundMaamary, J., Array, F., Gao, Q., García-Sastre, A., Steinman, R., Palese, P., & Nchinda, G. (2010) · Journal of Virology · doi:10.1128/jvi.02036-10 · Cited by 45 · see citing works
“DEC205 is an endocytic receptor of the macrophage mannose receptor family and is expressed on DCs in the T cell area of lymphoid organs (15).”
BackgroundSelf-citationThe Polymorphisms in DC-SIGNR Affect Susceptibility to HIV Type 1 Infection
Wichukchinda, N., Kitamura, Y., Rojanawiwat, A., Nakayama, E., Song, H.-H., Pathipvanich, P., Auwanit, W., Sawanpanyalert, P., Iwamoto, A., Shioda, T., et al. (2007) · AIDS Research and Human Retroviruses · doi:10.1089/aid.2006.0212 · Cited by 45
Strokappe, N. M., Hock, M., Rutten, L., McCoy, L. E., Back, J. W., Caillat, C., Haffke, M., Weiss, R. A., Weissenhorn, W., & Verrips, T. C. (2019) · Antibodies · doi:10.3390/antib8020038 · Cited by 44 · see citing works
“While antiretroviral therapy and careful clinical management can render HIV a chronic disease, the treatment is expensive and has many adverse effects [1].”
BackgroundFungal Surface and Innate Immune Recognition of Filamentous Fungi
Figueiredo, R., Carneiro, L., & Bozza, M. (2011) · Front. Microbio. · doi:10.3389/fmicb.2011.00248 · Cited by 42 · see citing works
“(Serrano-Gómez et al., 2004).”
BackgroundZuidwijk, K., de Fijter, J., Mallat, M., Eikmans, M., van Groningen, M. V., Goemaere, N., Bajema, I., & van Kooten, C. (2012) · Kidney International · doi:10.1038/ki.2011.289 · Cited by 41 · see citing works
Syndecan-3 in Inflammation and Angiogenesis
Arokiasamy, S., Balderstone, M. J. M., Rossi, G. D., & Whiteford, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2019.03031 · Cited by 40
Njongmeta, L., Bray, J., Davies, C., Davis, W., Howard, C., Hope, J., Palmer, G., Brown, W., & Mwangi, W. (2012) · Vaccine · doi:10.1016/j.vaccine.2011.12.110 · Cited by 40
- Authors
- Granelli-Piperno, A., Pritsker, A., Pack, M., Shimeliovich, I., Arrighi, J.-F., Park, C. G., Trumpfheller, C., Piguet, V., Moran, T. M., & Steinman, R. M.
- Affiliations
- Laboratory of Cellular Physiology and Immunology and Chris Browne Center for Immunology and Immune Diseases, Rockefeller University , New York, NY 10021
- Icahn School of Medicine at Mount Sinai (US)
- Rockefeller University (US)
- University Hospital of Geneva (CH)
- Corresponding author
- Pack, Maggi
- Shimeliovich, Irina
- Trumpfheller, Christine
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-10-01
- Volume
- 175
- Issue
- 7
- Pages
- 4265-4273
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1646818583
- Cited by
- 208
- References
- 0
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 6 · 2021: 7 · 2020: 3 · 2019: 7 · 2018: 3 · 2017: 3 · 2016: 5 · 2015: 3 · 2014: 9 · 2013: 15 · 2012: 15
- FWCI
- 8.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons - RU (Rockefeller University) (submittedVersion)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (2m01rr000102-41)
- National Institute of Allergy and Infectious Diseases (R01 AI40045, 5P30AI42848-04, P30AI042848, R01AI040045)
- National Center for Research Resources (M01-RR000102, M0-1 RR00102)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- DC-SIGN, C-type lectin, macrophages, lymph nodes, HIV-1 transmission, dendritic cells, mixed lymphocyte reaction, T cell proliferation, IL-4, monocytes
- MeSH terms
- DC-Specific ICAM-3 Grabbing Nonintegrin, Animals, Antibodies, Monoclonal, Cell Line, Clone Cells, Dendritic Cells, Dogs, Humans, Lymphocyte Culture Test, Mixed, Lymph Nodes, Macrophages, Mice, Inbred BALB C, Receptors, Cell Surface, Recombinant Proteins, T-Lymphocytes, Transfection, HIV-1, Cell Adhesion Molecules, RNA, Small Interfering, Lectins, C-Type, Mice
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