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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 tetramers enhance NK-cell activation. (A) Purified NK cells were stimulated by S100A9 tetramers or S100A9 monomers at 1 μg/ml during 4 h, then CD69 expression was assessed; graph shows cumulative results from five independent experiments. (B) Purified NK cells were stimulated by S100A9 tetramers or S100A9 monomers at 1 μg/ml during 4 days, then CD69 expression was assessed; graph shows cumulative results from seven independent experiments. (C) Schema depicts the protocol used in (D), 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; finally, 96 h (4 days) later, CD69 expression on NK cells was analyzed. (D) Graph shows cumulative results from five independent experiments. Results are expressed as mean ± SE and p values are shown. A9M, S100A9 monomer; A9T, S100A9 tetramer; DCn.i., non-infected DC; DC-MVAWT, MVAWT-infected DC; DC-MVAHIV, MVAHIV-infected DC.
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Figure 1: S100A9 tetramers enhance NK-cell activation. (A) Purified NK cells were stimulated by S100A9 tetramers or S100A9 monomers at 1 μg/ml during 4 h, then CD69 expression was assessed; graph shows cumulative results from five independent experiments. (B) Purified NK cells were stimulated by S100A9 tetramers or S100A9 monomers at 1 μg/ml during 4 days, then CD69 expression was assessed; graph shows cumulative results from seven independent experiments. (C) Schema depicts the protocol used in (D), 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; finally, 96 h (4 days) later, CD69 expression on NK cells was analyzed. (D) Graph shows cumulative results from five independent experiments. Results are expressed as mean ± SE and p values are shown. A9M, S100A9 monomer; A9T, S100A9 tetramer; DCn.i., non-infected DC; DC-MVAWT, MVAWT-infected DC; DC-MVAHIV, MVAHIV-infected DC.

Mentions: We previously showed that stimulation of NK cells by S100A9 tetramers enhances the early responsiveness against target cells and the control of HIV infection in CD4+ T cells (10). Here, we first analyzed whether S100A9 tetramers modulate the activation of NK cells (Figure 1). We observed that 4-h stimulation of PBMCs (data not shown) or purified NK cells (Figure 1A) by S100A9 tetramers enhanced the activation of NK cells, assessed by the expression of the activation marker CD69, whereas stimulation of NK cells by S100A9 monomers had no effect. Moreover, we observed that 4-day stimulation of NK cells by S100A9 tetramers also resulted in higher NK-cell activation (Figure 1B).


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 tetramers enhance NK-cell activation. (A) Purified NK cells were stimulated by S100A9 tetramers or S100A9 monomers at 1 μg/ml during 4 h, then CD69 expression was assessed; graph shows cumulative results from five independent experiments. (B) Purified NK cells were stimulated by S100A9 tetramers or S100A9 monomers at 1 μg/ml during 4 days, then CD69 expression was assessed; graph shows cumulative results from seven independent experiments. (C) Schema depicts the protocol used in (D), 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; finally, 96 h (4 days) later, CD69 expression on NK cells was analyzed. (D) Graph shows cumulative results from five independent experiments. Results are expressed as mean ± SE and p values are shown. A9M, S100A9 monomer; A9T, S100A9 tetramer; DCn.i., non-infected DC; DC-MVAWT, MVAWT-infected DC; DC-MVAHIV, MVAHIV-infected DC.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: S100A9 tetramers enhance NK-cell activation. (A) Purified NK cells were stimulated by S100A9 tetramers or S100A9 monomers at 1 μg/ml during 4 h, then CD69 expression was assessed; graph shows cumulative results from five independent experiments. (B) Purified NK cells were stimulated by S100A9 tetramers or S100A9 monomers at 1 μg/ml during 4 days, then CD69 expression was assessed; graph shows cumulative results from seven independent experiments. (C) Schema depicts the protocol used in (D), 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; finally, 96 h (4 days) later, CD69 expression on NK cells was analyzed. (D) Graph shows cumulative results from five independent experiments. Results are expressed as mean ± SE and p values are shown. A9M, S100A9 monomer; A9T, S100A9 tetramer; DCn.i., non-infected DC; DC-MVAWT, MVAWT-infected DC; DC-MVAHIV, MVAHIV-infected DC.
Mentions: We previously showed that stimulation of NK cells by S100A9 tetramers enhances the early responsiveness against target cells and the control of HIV infection in CD4+ T cells (10). Here, we first analyzed whether S100A9 tetramers modulate the activation of NK cells (Figure 1). We observed that 4-h stimulation of PBMCs (data not shown) or purified NK cells (Figure 1A) by S100A9 tetramers enhanced the activation of NK cells, assessed by the expression of the activation marker CD69, whereas stimulation of NK cells by S100A9 monomers had no effect. Moreover, we observed that 4-day stimulation of NK cells by S100A9 tetramers also resulted in higher NK-cell activation (Figure 1B).

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