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S100A9 Tetramers, Which are Ligands of CD85j, Increase the Ability of MVAHIV-Primed NK Cells to Control HIV Infection.

Moreno-Nieves UY, Didier C, Lévy Y, Barré-Sinoussi F, Scott-Algara D, ANRS HIV Vaccine Network (AHV - Front Immunol (2015)

Bottom Line: Natural killer (NK) cells are the major antiviral effector population of the innate immune system.We previously found that S100A9 is a novel ligand of the receptor CD85j and that S100A9 tetramers enhance the anti-HIV activity of NK cells.We found that S100A9 tetramers activate NK cells and that DCs enhance the anti-HIV activity of NK cells.

View Article: PubMed Central - PubMed

Affiliation: Unité de Régulation des Infections Rétrovirales, Department of Virology, Institut Pasteur , Paris , France.

ABSTRACT
Natural killer (NK) cells are the major antiviral effector population of the innate immune system. We previously found that S100A9 is a novel ligand of the receptor CD85j and that S100A9 tetramers enhance the anti-HIV activity of NK cells. Also, we found that dendritic cells (DCs) infected by the HIV vaccine candidate, MVAHIV, prime NK cells to specifically control HIV infection in autologous CD4(+) T cells. In this study, we analyzed whether stimulation of NK cells by S100A9 tetramers prior to the priming by MVAHIV-infected DCs modulates the subsequent anti-HIV activity of NK cells. We found that S100A9 tetramers activate NK cells and that DCs enhance the anti-HIV activity of NK cells. Interestingly, we observed that stimulation of NK cells by S100A9 tetramers, prior to the priming, significantly increased the subsequent anti-HIV activity of NK cells and that the enhanced anti-HIV activity was observed following different conditions of priming, including the MVAHIV-priming. As S100A9 tetramers alone directly increase the anti-HIV activity of NK cells and as this increased anti-HIV activity is also observed following the interaction of NK cells with MVAHIV-infected DCs, we propose S100A9 tetramers as potential adjuvants to stimulate the anti-HIV activity of NK cells.

No MeSH data available.


Related in: MedlinePlus

S100A9-tetramer stimulation prior to the priming by DCs enhances the anti-HIV response of NK cells. S100A9-stimulated and MVA-primed NK cells were tested in their ability to degranulate (express CD107a) and produce IFN-γ in response to HIV-infected autologous CD4+ T cells. (A) Schema depicts the protocol used in (B,C), in brief: DCs were infected or not by MVAWT or MVAHIV, and 24 h later non-infected DCs and S100A9-stimulated NK cells were added to the culture; and 96 h later (4 days) NK cells were transferred to a culture of HIV-infected CD4+ T cells and the degranulation and IFN-γ production were assessed. (B,C) Graphs show the percentage of CD107a+(B) and IFN-γ+(C) NK cells; cumulative results from six independent experiments are shown as mean ± SE and p values are shown. A9M, S100A9 monomer; A9T, S100A9 tetramer; DC-MVAWT, MVAWT-infected DC; DC-MVAHIV, MVAHIV-infected DC.
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Figure 3: S100A9-tetramer stimulation prior to the priming by DCs enhances the anti-HIV response of NK cells. S100A9-stimulated and MVA-primed NK cells were tested in their ability to degranulate (express CD107a) and produce IFN-γ in response to HIV-infected autologous CD4+ T cells. (A) Schema depicts the protocol used in (B,C), in brief: DCs were infected or not by MVAWT or MVAHIV, and 24 h later non-infected DCs and S100A9-stimulated NK cells were added to the culture; and 96 h later (4 days) NK cells were transferred to a culture of HIV-infected CD4+ T cells and the degranulation and IFN-γ production were assessed. (B,C) Graphs show the percentage of CD107a+(B) and IFN-γ+(C) NK cells; cumulative results from six independent experiments are shown as mean ± SE and p values are shown. A9M, S100A9 monomer; A9T, S100A9 tetramer; DC-MVAWT, MVAWT-infected DC; DC-MVAHIV, MVAHIV-infected DC.

Mentions: Natural killer cells use several mechanisms to control viral infections, such as the secretion of antiviral cytokines (e.g., IFN-γ) and the release of lytic proteins contained in granules (i.e., degranulation). Therefore, we analyzed the capacity of NK cells primed under the above-mentioned conditions to degranulate and produce cytokines against HIV-infected autologous CD4+ T cells (Figure 3). Briefly, after the 4-day priming, NK cells were collected and incubated with HIV-infected CD4+ T cells (Figure 3A), and the degranulation (CD107a expression; Figure 3B) and the production of IFN-γ (Figure 3C) and TNF-α (data not shown) were assessed. As we previously reported (11), NK cells primed by MVAWT- and MVAHIV-infected DCs degranulate higher (Figure 3B) and trended to produce more IFN-γ (Figure 3C) against HIV-infected CD4+ T cells compared with NK cells primed by non-infected DCs. Interestingly, we observed that pre-stimulation of NK cells by S100A9 tetramers, but not S100A9 monomers, resulted in significantly increased degranulation (Figure 3B) and IFN-γ production (Figure 3C) after the priming, independently of the priming condition. Pre-stimulation of NK cells by S100A9 proteins did not modulate the TNF-α production by NK cells in response to HIV-infected CD4+ T cells (data not shown). Additionally, in these conditions, we analyzed the NK-cell response against the MHC-I-deficient K562 target cell (data not shown); we found that pre-stimulation of NK cells by S100A9 monomers or S100A9 tetramers did not modulate the NK-cell response against K562 cells in terms of degranulation and cytokine production. Overall, these results showed that stimulation of NK cells by S100A9 tetramers prior to the priming by DCs lead to increased early NK-cell response against HIV-infected CD4+ T cells after the priming.


S100A9 Tetramers, Which are Ligands of CD85j, Increase the Ability of MVAHIV-Primed NK Cells to Control HIV Infection.

Moreno-Nieves UY, Didier C, Lévy Y, Barré-Sinoussi F, Scott-Algara D, ANRS HIV Vaccine Network (AHV - Front Immunol (2015)

S100A9-tetramer stimulation prior to the priming by DCs enhances the anti-HIV response of NK cells. S100A9-stimulated and MVA-primed NK cells were tested in their ability to degranulate (express CD107a) and produce IFN-γ in response to HIV-infected autologous CD4+ T cells. (A) Schema depicts the protocol used in (B,C), in brief: DCs were infected or not by MVAWT or MVAHIV, and 24 h later non-infected DCs and S100A9-stimulated NK cells were added to the culture; and 96 h later (4 days) NK cells were transferred to a culture of HIV-infected CD4+ T cells and the degranulation and IFN-γ production were assessed. (B,C) Graphs show the percentage of CD107a+(B) and IFN-γ+(C) NK cells; cumulative results from six independent experiments are shown as mean ± SE and p values are shown. A9M, S100A9 monomer; A9T, S100A9 tetramer; DC-MVAWT, MVAWT-infected DC; DC-MVAHIV, MVAHIV-infected DC.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4585218&req=5

Figure 3: S100A9-tetramer stimulation prior to the priming by DCs enhances the anti-HIV response of NK cells. S100A9-stimulated and MVA-primed NK cells were tested in their ability to degranulate (express CD107a) and produce IFN-γ in response to HIV-infected autologous CD4+ T cells. (A) Schema depicts the protocol used in (B,C), in brief: DCs were infected or not by MVAWT or MVAHIV, and 24 h later non-infected DCs and S100A9-stimulated NK cells were added to the culture; and 96 h later (4 days) NK cells were transferred to a culture of HIV-infected CD4+ T cells and the degranulation and IFN-γ production were assessed. (B,C) Graphs show the percentage of CD107a+(B) and IFN-γ+(C) NK cells; cumulative results from six independent experiments are shown as mean ± SE and p values are shown. A9M, S100A9 monomer; A9T, S100A9 tetramer; DC-MVAWT, MVAWT-infected DC; DC-MVAHIV, MVAHIV-infected DC.
Mentions: Natural killer cells use several mechanisms to control viral infections, such as the secretion of antiviral cytokines (e.g., IFN-γ) and the release of lytic proteins contained in granules (i.e., degranulation). Therefore, we analyzed the capacity of NK cells primed under the above-mentioned conditions to degranulate and produce cytokines against HIV-infected autologous CD4+ T cells (Figure 3). Briefly, after the 4-day priming, NK cells were collected and incubated with HIV-infected CD4+ T cells (Figure 3A), and the degranulation (CD107a expression; Figure 3B) and the production of IFN-γ (Figure 3C) and TNF-α (data not shown) were assessed. As we previously reported (11), NK cells primed by MVAWT- and MVAHIV-infected DCs degranulate higher (Figure 3B) and trended to produce more IFN-γ (Figure 3C) against HIV-infected CD4+ T cells compared with NK cells primed by non-infected DCs. Interestingly, we observed that pre-stimulation of NK cells by S100A9 tetramers, but not S100A9 monomers, resulted in significantly increased degranulation (Figure 3B) and IFN-γ production (Figure 3C) after the priming, independently of the priming condition. Pre-stimulation of NK cells by S100A9 proteins did not modulate the TNF-α production by NK cells in response to HIV-infected CD4+ T cells (data not shown). Additionally, in these conditions, we analyzed the NK-cell response against the MHC-I-deficient K562 target cell (data not shown); we found that pre-stimulation of NK cells by S100A9 monomers or S100A9 tetramers did not modulate the NK-cell response against K562 cells in terms of degranulation and cytokine production. Overall, these results showed that stimulation of NK cells by S100A9 tetramers prior to the priming by DCs lead to increased early NK-cell response against HIV-infected CD4+ T cells after the priming.

Bottom Line: Natural killer (NK) cells are the major antiviral effector population of the innate immune system.We previously found that S100A9 is a novel ligand of the receptor CD85j and that S100A9 tetramers enhance the anti-HIV activity of NK cells.We found that S100A9 tetramers activate NK cells and that DCs enhance the anti-HIV activity of NK cells.

View Article: PubMed Central - PubMed

Affiliation: Unité de Régulation des Infections Rétrovirales, Department of Virology, Institut Pasteur , Paris , France.

ABSTRACT
Natural killer (NK) cells are the major antiviral effector population of the innate immune system. We previously found that S100A9 is a novel ligand of the receptor CD85j and that S100A9 tetramers enhance the anti-HIV activity of NK cells. Also, we found that dendritic cells (DCs) infected by the HIV vaccine candidate, MVAHIV, prime NK cells to specifically control HIV infection in autologous CD4(+) T cells. In this study, we analyzed whether stimulation of NK cells by S100A9 tetramers prior to the priming by MVAHIV-infected DCs modulates the subsequent anti-HIV activity of NK cells. We found that S100A9 tetramers activate NK cells and that DCs enhance the anti-HIV activity of NK cells. Interestingly, we observed that stimulation of NK cells by S100A9 tetramers, prior to the priming, significantly increased the subsequent anti-HIV activity of NK cells and that the enhanced anti-HIV activity was observed following different conditions of priming, including the MVAHIV-priming. As S100A9 tetramers alone directly increase the anti-HIV activity of NK cells and as this increased anti-HIV activity is also observed following the interaction of NK cells with MVAHIV-infected DCs, we propose S100A9 tetramers as potential adjuvants to stimulate the anti-HIV activity of NK cells.

No MeSH data available.


Related in: MedlinePlus