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DC-SIGN and CD150 have distinct roles in transmission of measles virus from dendritic cells to T-lymphocytes.

de Witte L, de Vries RD, van der Vlist M, Yüksel S, Litjens M, de Swart RL, Geijtenbeek TB - PLoS Pathog. (2008)

Bottom Line: Using immunofluorescence microscopy, we demonstrate that DC-SIGN+ DCs are abundantly present just below the epithelia of the respiratory tract.DC-SIGN+ DCs efficiently present MV-derived antigens to CD4+ T-lymphocytes after antigen uptake via either CD150 or DC-SIGN in vitro.However, DC-SIGN+ DCs also mediate transmission of MV to CD4+ and CD8+ T-lymphocytes.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.

ABSTRACT
Measles virus (MV) is among the most infectious viruses that affect humans and is transmitted via the respiratory route. In macaques, MV primarily infects lymphocytes and dendritic cells (DCs). Little is known about the initial target cell for MV infection. Since DCs bridge the peripheral mucosal tissues with lymphoid tissues, we hypothesize that DCs are the initial target cells that capture MV in the respiratory tract and transport the virus to the lymphoid tissues where MV is transmitted to lymphocytes. Recently, we have demonstrated that the C-type lectin DC-SIGN interacts with MV and enhances infection of DCs in cis. Using immunofluorescence microscopy, we demonstrate that DC-SIGN+ DCs are abundantly present just below the epithelia of the respiratory tract. DC-SIGN+ DCs efficiently present MV-derived antigens to CD4+ T-lymphocytes after antigen uptake via either CD150 or DC-SIGN in vitro. However, DC-SIGN+ DCs also mediate transmission of MV to CD4+ and CD8+ T-lymphocytes. We distinguished two different transmission routes that were either dependent or independent on direct DC infection. DC-SIGN and CD150 are both involved in direct DC infection and subsequent transmission of de novo synthesized virus. However, DC-SIGN, but not CD150, mediates trans-infection of MV to T-lymphocytes independent of DC infection. Together these data suggest a prominent role for DCs during the initiation, dissemination, and clearance of MV infection.

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DC-SIGN+-dendritic cells are present in the sub-epithelial tissues of the respiratory tract.(A,B) Cryosections of different tissues from healthy donors were stained for the expression of DC-SIGN (green) and CD150 (red) using specific antibodies, and for the nuclei using Hoechst (blue). The sections were analyzed by fluorescence microscopy. (A,B) Representative photos with a magnification of 100× are depicted (e = epithelium; s = sub-epithelial tissue, i = inter-follicular, f = follicles, m = medullary sinus, p = paracortex, arrow = autofluorescence, * = co-localization).
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ppat-1000049-g001: DC-SIGN+-dendritic cells are present in the sub-epithelial tissues of the respiratory tract.(A,B) Cryosections of different tissues from healthy donors were stained for the expression of DC-SIGN (green) and CD150 (red) using specific antibodies, and for the nuclei using Hoechst (blue). The sections were analyzed by fluorescence microscopy. (A,B) Representative photos with a magnification of 100× are depicted (e = epithelium; s = sub-epithelial tissue, i = inter-follicular, f = follicles, m = medullary sinus, p = paracortex, arrow = autofluorescence, * = co-localization).

Mentions: DC-SIGN was abundantly present in buccal, pharyngeal, tonsillar, tracheal and bronchial sub-epithelial tissues (Figure 1A and S1, Table 1). Similar to previous reports [15], scattered DC-SIGN+ DCs were also observed in the lungs, mainly in the interstitium of the alveoli (Table 1).


DC-SIGN and CD150 have distinct roles in transmission of measles virus from dendritic cells to T-lymphocytes.

de Witte L, de Vries RD, van der Vlist M, Yüksel S, Litjens M, de Swart RL, Geijtenbeek TB - PLoS Pathog. (2008)

DC-SIGN+-dendritic cells are present in the sub-epithelial tissues of the respiratory tract.(A,B) Cryosections of different tissues from healthy donors were stained for the expression of DC-SIGN (green) and CD150 (red) using specific antibodies, and for the nuclei using Hoechst (blue). The sections were analyzed by fluorescence microscopy. (A,B) Representative photos with a magnification of 100× are depicted (e = epithelium; s = sub-epithelial tissue, i = inter-follicular, f = follicles, m = medullary sinus, p = paracortex, arrow = autofluorescence, * = co-localization).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2277461&req=5

ppat-1000049-g001: DC-SIGN+-dendritic cells are present in the sub-epithelial tissues of the respiratory tract.(A,B) Cryosections of different tissues from healthy donors were stained for the expression of DC-SIGN (green) and CD150 (red) using specific antibodies, and for the nuclei using Hoechst (blue). The sections were analyzed by fluorescence microscopy. (A,B) Representative photos with a magnification of 100× are depicted (e = epithelium; s = sub-epithelial tissue, i = inter-follicular, f = follicles, m = medullary sinus, p = paracortex, arrow = autofluorescence, * = co-localization).
Mentions: DC-SIGN was abundantly present in buccal, pharyngeal, tonsillar, tracheal and bronchial sub-epithelial tissues (Figure 1A and S1, Table 1). Similar to previous reports [15], scattered DC-SIGN+ DCs were also observed in the lungs, mainly in the interstitium of the alveoli (Table 1).

Bottom Line: Using immunofluorescence microscopy, we demonstrate that DC-SIGN+ DCs are abundantly present just below the epithelia of the respiratory tract.DC-SIGN+ DCs efficiently present MV-derived antigens to CD4+ T-lymphocytes after antigen uptake via either CD150 or DC-SIGN in vitro.However, DC-SIGN+ DCs also mediate transmission of MV to CD4+ and CD8+ T-lymphocytes.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.

ABSTRACT
Measles virus (MV) is among the most infectious viruses that affect humans and is transmitted via the respiratory route. In macaques, MV primarily infects lymphocytes and dendritic cells (DCs). Little is known about the initial target cell for MV infection. Since DCs bridge the peripheral mucosal tissues with lymphoid tissues, we hypothesize that DCs are the initial target cells that capture MV in the respiratory tract and transport the virus to the lymphoid tissues where MV is transmitted to lymphocytes. Recently, we have demonstrated that the C-type lectin DC-SIGN interacts with MV and enhances infection of DCs in cis. Using immunofluorescence microscopy, we demonstrate that DC-SIGN+ DCs are abundantly present just below the epithelia of the respiratory tract. DC-SIGN+ DCs efficiently present MV-derived antigens to CD4+ T-lymphocytes after antigen uptake via either CD150 or DC-SIGN in vitro. However, DC-SIGN+ DCs also mediate transmission of MV to CD4+ and CD8+ T-lymphocytes. We distinguished two different transmission routes that were either dependent or independent on direct DC infection. DC-SIGN and CD150 are both involved in direct DC infection and subsequent transmission of de novo synthesized virus. However, DC-SIGN, but not CD150, mediates trans-infection of MV to T-lymphocytes independent of DC infection. Together these data suggest a prominent role for DCs during the initiation, dissemination, and clearance of MV infection.

Show MeSH
Related in: MedlinePlus