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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

Following S100A9-tetramer stimulation, NK cells moderately respond higher against DCs. NK cells were stimulated or not by S100A9 tetramers or S100A9 monomers at 1 μg/ml during 4 h, then NK cells were cultured with DCs infected or not by MVAWT or MVAHIV. After 4 h of coculture, the degranulation (CD107a surface expression) and intracellular IFN-γ production were analyzed on gated NK cells. (A,B) Graphs show the percentage of IFN-γ+(A) and CD107a+(B) NK cells; cumulative results from four independent experiments are shown. Results are expressed as mean ± SE and p values are shown. (C,D) Graphs show the percentage increase in IFN-γ+(C) and CD107a+(D) expression on S100A9-stimulated NK cells compared with unstimulated NK cells; cumulative results from four independent experiments are shown. Results are expressed as whiskers with minimum and maximum. A9M, S100A9 monomer; A9T, S100A9 tetramer; DCni, non-infected DC; DC-MVAWT, MVAWT-infected DC; DC-MVAHIV, MVAHIV-infected DC.
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Figure 2: Following S100A9-tetramer stimulation, NK cells moderately respond higher against DCs. NK cells were stimulated or not by S100A9 tetramers or S100A9 monomers at 1 μg/ml during 4 h, then NK cells were cultured with DCs infected or not by MVAWT or MVAHIV. After 4 h of coculture, the degranulation (CD107a surface expression) and intracellular IFN-γ production were analyzed on gated NK cells. (A,B) Graphs show the percentage of IFN-γ+(A) and CD107a+(B) NK cells; cumulative results from four independent experiments are shown. Results are expressed as mean ± SE and p values are shown. (C,D) Graphs show the percentage increase in IFN-γ+(C) and CD107a+(D) expression on S100A9-stimulated NK cells compared with unstimulated NK cells; cumulative results from four independent experiments are shown. Results are expressed as whiskers with minimum and maximum. A9M, S100A9 monomer; A9T, S100A9 tetramer; DCni, non-infected DC; DC-MVAWT, MVAWT-infected DC; DC-MVAHIV, MVAHIV-infected DC.

Mentions: Next, we investigated whether S100A9 tetramers modulate NK-cell and DC responses during the priming. We analyzed the early cytokine production and degranulation of S100A9-stimulated NK cells against DCs infected or not by MVA (Figure 2). As previously described (15), we observed that NK cells produce more intracellular IFN-γ (Figure 2A) and higher degranulation (Figure 2B) against MVAWT- and MVAHIV-infected DCs compared with non-infected DCs and that stimulation of NK cells by S100A9 tetramers trended to enhance IFN-γ production (Figure 2C) and degranulation (Figure 2D). Pre-stimulation of NK cells by S100A9 monomers had no effect on the early NK-cell response to DCs. Study of the NK-cell receptor repertoire expression at different time points during the coculture, from 12 to 96 h (Figure S3 in Supplementary Material and data not shown), showed that stimulation of NK cells by S100A9 tetramers, but not S100A9 monomers, resulted in a trended lower expression of NKG2C (Figure S3A in Supplementary Material) and trended decreased expression of NKG2D (Figure S3B in Supplementary Material). The analysis of NK-cell proliferation showed that pre-stimulation of NK cells by S100A9 monomers or S100A9 tetramers did not modify NK-cell proliferation (data not shown).


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)

Following S100A9-tetramer stimulation, NK cells moderately respond higher against DCs. NK cells were stimulated or not by S100A9 tetramers or S100A9 monomers at 1 μg/ml during 4 h, then NK cells were cultured with DCs infected or not by MVAWT or MVAHIV. After 4 h of coculture, the degranulation (CD107a surface expression) and intracellular IFN-γ production were analyzed on gated NK cells. (A,B) Graphs show the percentage of IFN-γ+(A) and CD107a+(B) NK cells; cumulative results from four independent experiments are shown. Results are expressed as mean ± SE and p values are shown. (C,D) Graphs show the percentage increase in IFN-γ+(C) and CD107a+(D) expression on S100A9-stimulated NK cells compared with unstimulated NK cells; cumulative results from four independent experiments are shown. Results are expressed as whiskers with minimum and maximum. A9M, S100A9 monomer; A9T, S100A9 tetramer; DCni, non-infected DC; DC-MVAWT, MVAWT-infected DC; DC-MVAHIV, MVAHIV-infected DC.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
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Figure 2: Following S100A9-tetramer stimulation, NK cells moderately respond higher against DCs. NK cells were stimulated or not by S100A9 tetramers or S100A9 monomers at 1 μg/ml during 4 h, then NK cells were cultured with DCs infected or not by MVAWT or MVAHIV. After 4 h of coculture, the degranulation (CD107a surface expression) and intracellular IFN-γ production were analyzed on gated NK cells. (A,B) Graphs show the percentage of IFN-γ+(A) and CD107a+(B) NK cells; cumulative results from four independent experiments are shown. Results are expressed as mean ± SE and p values are shown. (C,D) Graphs show the percentage increase in IFN-γ+(C) and CD107a+(D) expression on S100A9-stimulated NK cells compared with unstimulated NK cells; cumulative results from four independent experiments are shown. Results are expressed as whiskers with minimum and maximum. A9M, S100A9 monomer; A9T, S100A9 tetramer; DCni, non-infected DC; DC-MVAWT, MVAWT-infected DC; DC-MVAHIV, MVAHIV-infected DC.
Mentions: Next, we investigated whether S100A9 tetramers modulate NK-cell and DC responses during the priming. We analyzed the early cytokine production and degranulation of S100A9-stimulated NK cells against DCs infected or not by MVA (Figure 2). As previously described (15), we observed that NK cells produce more intracellular IFN-γ (Figure 2A) and higher degranulation (Figure 2B) against MVAWT- and MVAHIV-infected DCs compared with non-infected DCs and that stimulation of NK cells by S100A9 tetramers trended to enhance IFN-γ production (Figure 2C) and degranulation (Figure 2D). Pre-stimulation of NK cells by S100A9 monomers had no effect on the early NK-cell response to DCs. Study of the NK-cell receptor repertoire expression at different time points during the coculture, from 12 to 96 h (Figure S3 in Supplementary Material and data not shown), showed that stimulation of NK cells by S100A9 tetramers, but not S100A9 monomers, resulted in a trended lower expression of NKG2C (Figure S3A in Supplementary Material) and trended decreased expression of NKG2D (Figure S3B in Supplementary Material). The analysis of NK-cell proliferation showed that pre-stimulation of NK cells by S100A9 monomers or S100A9 tetramers did not modify NK-cell proliferation (data not shown).

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