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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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Trans-infection of measles virus by dendritic cells is dependent on DC-SIGN, but not on CD150.(A–D) DCs (5×104 cells) or (B) T-lymphocytes from different donors were pre-incubated with mannan, anti-DC-SIGN or anti-CD150 (for donor #1 and #2), before incubation with MV-IC323-EGFP (5×104 TCID50). (A) The cells were cultured in the presence of FIP for 3 days and analyzed by flow cytometry. (B–D) After 2 hours the cells were washed and T-lymphocytes (2×105 cells) were added. For donor #5–7 autologous T-lymphocytes were used as target cells. The fusion inhibitory peptide (FIP) was added after 2 hours. After 72 hours the cultures were analyzed by flow cytometry. (B) Transmission by different donors of DCs is depicted. As a control for the specificity of mannan and anti-DC-SIGN T-lymphocytes were pre-treated and directly infected. Error bars represent the standard deviation of triplicates. (C) The results of the different donors in (B) (#1–7) were normalized to the medium control to determine the statistical differences by ANOVA. Error bars represent the standard deviation of the mean of the different donors, *** = p<0,01 versus the medium control.
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ppat-1000049-g005: Trans-infection of measles virus by dendritic cells is dependent on DC-SIGN, but not on CD150.(A–D) DCs (5×104 cells) or (B) T-lymphocytes from different donors were pre-incubated with mannan, anti-DC-SIGN or anti-CD150 (for donor #1 and #2), before incubation with MV-IC323-EGFP (5×104 TCID50). (A) The cells were cultured in the presence of FIP for 3 days and analyzed by flow cytometry. (B–D) After 2 hours the cells were washed and T-lymphocytes (2×105 cells) were added. For donor #5–7 autologous T-lymphocytes were used as target cells. The fusion inhibitory peptide (FIP) was added after 2 hours. After 72 hours the cultures were analyzed by flow cytometry. (B) Transmission by different donors of DCs is depicted. As a control for the specificity of mannan and anti-DC-SIGN T-lymphocytes were pre-treated and directly infected. Error bars represent the standard deviation of triplicates. (C) The results of the different donors in (B) (#1–7) were normalized to the medium control to determine the statistical differences by ANOVA. Error bars represent the standard deviation of the mean of the different donors, *** = p<0,01 versus the medium control.

Mentions: DC-SIGN and CD150 are both important for binding of MV to DCs and subsequent infection. Indeed, MV-infection of DCs is inhibited by antibodies against CD150 and DC-SIGN, as well as by mannan (Figure 5A) [11]. MV transmission by de novo synthesis of MV particles depends on infection of DCs and therefore these data suggest that transmission through de novo synthesis of virus is dependent on both CD150 and DC-SIGN.


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)

Trans-infection of measles virus by dendritic cells is dependent on DC-SIGN, but not on CD150.(A–D) DCs (5×104 cells) or (B) T-lymphocytes from different donors were pre-incubated with mannan, anti-DC-SIGN or anti-CD150 (for donor #1 and #2), before incubation with MV-IC323-EGFP (5×104 TCID50). (A) The cells were cultured in the presence of FIP for 3 days and analyzed by flow cytometry. (B–D) After 2 hours the cells were washed and T-lymphocytes (2×105 cells) were added. For donor #5–7 autologous T-lymphocytes were used as target cells. The fusion inhibitory peptide (FIP) was added after 2 hours. After 72 hours the cultures were analyzed by flow cytometry. (B) Transmission by different donors of DCs is depicted. As a control for the specificity of mannan and anti-DC-SIGN T-lymphocytes were pre-treated and directly infected. Error bars represent the standard deviation of triplicates. (C) The results of the different donors in (B) (#1–7) were normalized to the medium control to determine the statistical differences by ANOVA. Error bars represent the standard deviation of the mean of the different donors, *** = p<0,01 versus the medium control.
© Copyright Policy
Related In: Results  -  Collection

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

ppat-1000049-g005: Trans-infection of measles virus by dendritic cells is dependent on DC-SIGN, but not on CD150.(A–D) DCs (5×104 cells) or (B) T-lymphocytes from different donors were pre-incubated with mannan, anti-DC-SIGN or anti-CD150 (for donor #1 and #2), before incubation with MV-IC323-EGFP (5×104 TCID50). (A) The cells were cultured in the presence of FIP for 3 days and analyzed by flow cytometry. (B–D) After 2 hours the cells were washed and T-lymphocytes (2×105 cells) were added. For donor #5–7 autologous T-lymphocytes were used as target cells. The fusion inhibitory peptide (FIP) was added after 2 hours. After 72 hours the cultures were analyzed by flow cytometry. (B) Transmission by different donors of DCs is depicted. As a control for the specificity of mannan and anti-DC-SIGN T-lymphocytes were pre-treated and directly infected. Error bars represent the standard deviation of triplicates. (C) The results of the different donors in (B) (#1–7) were normalized to the medium control to determine the statistical differences by ANOVA. Error bars represent the standard deviation of the mean of the different donors, *** = p<0,01 versus the medium control.
Mentions: DC-SIGN and CD150 are both important for binding of MV to DCs and subsequent infection. Indeed, MV-infection of DCs is inhibited by antibodies against CD150 and DC-SIGN, as well as by mannan (Figure 5A) [11]. MV transmission by de novo synthesis of MV particles depends on infection of DCs and therefore these data suggest that transmission through de novo synthesis of virus is dependent on both CD150 and DC-SIGN.

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