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Both conventional and interferon killer dendritic cells have antigen-presenting capacity during influenza virus infection.

GeurtsvanKessel CH, Bergen IM, Muskens F, Boon L, Hoogsteden HC, Osterhaus AD, Rimmelzwaan GF, Lambrecht BN - PLoS ONE (2009)

Bottom Line: Here, using a model of influenza infection, we found recruitment of both conventional B220(-) NK cells and IKDCs to the lung.In vivo, the depletion of NK1.1-positive NK cells and IKDCs reduced the expansion of viral nucleoprotein-specific CD8 T cells in the lung and spleen, but did finally not affect viral clearance from the lung.In conclusion, we found evidence for APC function of lung NK cells during influenza infection, but this is a feature not exclusive to the IKDC subset.

View Article: PubMed Central - PubMed

Affiliation: Department of Pulmonary Medicine, Erasmus University Medical Centre, Rotterdam, The Netherlands.

ABSTRACT
Natural killer cells are innate effector cells known for their potential to produce interferon-gamma and kill tumour and virus-infected cells. Recently, B220(+)CD11c(int)NK1.1(+) NK cells were found to also have antigen-presenting capacity like dendritic cells (DC), hence their name interferon-producing killer DC (IKDC). Shortly after discovery, it has already been questioned if IKDC really represent a separate subset of NK cells or merely represent a state of activation. Despite similarities with DCs, in vivo evidence that they behave as bona fide APCs is lacking. Here, using a model of influenza infection, we found recruitment of both conventional B220(-) NK cells and IKDCs to the lung. To study antigen-presenting capacity of NK cell subsets and compare it to cDCs, all cell subsets were sorted from lungs of infected mice and co-cultured ex vivo with antigen specific T cells. Both IKDCs and conventional NK cells as well as cDCs presented virus-encoded antigen to CD8 T cells, whereas only cDCs presented to CD4 T cells. The absence of CD4 responses was predominantly due to a deficiency in MHCII processing, as preprocessed peptide antigen was presented equally well by cDCs and IKDCs. In vivo, the depletion of NK1.1-positive NK cells and IKDCs reduced the expansion of viral nucleoprotein-specific CD8 T cells in the lung and spleen, but did finally not affect viral clearance from the lung. In conclusion, we found evidence for APC function of lung NK cells during influenza infection, but this is a feature not exclusive to the IKDC subset.

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Kinetics of increase in IKDCs, B220−NK cells, and cDCs in lung tissue after influenza virus infection.(A) Cell populations were gated as demonstrated in Figure 1. Histograms demonstrate absolute numbers of IKDCs, B220−NK cells and cDCs at different time points after infection. Bars represent mean values +/− SEM of at least 5 mice per group. CD86 (B) and MHCII (C) expression on cell populations at 4 dpi expressed as mean MFI +/− SEM, derived from at least five mice per group. Similar results were obtained from three separate experiments (D) Gene expression analysis using Aff ymetrix GeneChips. Top heat map shows NK related chemokines and growth factors. Lower map shows NK related gene products.
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pone-0007187-g003: Kinetics of increase in IKDCs, B220−NK cells, and cDCs in lung tissue after influenza virus infection.(A) Cell populations were gated as demonstrated in Figure 1. Histograms demonstrate absolute numbers of IKDCs, B220−NK cells and cDCs at different time points after infection. Bars represent mean values +/− SEM of at least 5 mice per group. CD86 (B) and MHCII (C) expression on cell populations at 4 dpi expressed as mean MFI +/− SEM, derived from at least five mice per group. Similar results were obtained from three separate experiments (D) Gene expression analysis using Aff ymetrix GeneChips. Top heat map shows NK related chemokines and growth factors. Lower map shows NK related gene products.

Mentions: As influenza X-31 infection is a mild infection localized in the respiratory tract, we studied the effect of infection on the number and maturation status of IKDCs in the respiratory tract (lung, bronchoalveolar compartment (BALf), mediastinal LN (MLN) and the spleen), using the multi-parameter gating strategy as above. A kinetic analysis at various days post infection (dpi) revealed that IKDCs, B220−NK cells and cDCs accumulated in the lungs with different kinetics and to different extents; IKDCs and cDCs peaking at 7dpi whereas NK cells were increased from day 1 to 7 post infection compared with mock infected mice (data shown for digested lung tissue). For clarity reasons we lumped CD11b+ and CD11b− cDCs together, but we have recently provided detail on this [13]. We next defined the co-stimulatory molecule expression on these various populations at 4 dpi. Whereas we could find an increased number of IKDCs in all compartments (Figure 3A depicts only the digested lung samples), the increase in expression of the maturation marker CD86 (Figure 3B) and expression of MHC class II (Figure 3C) molecules was restricted to the site of primary infection being lung and BALf (figures depict lung tissue) and occurred on both IKDCs, B220−NK cells and cDCs, albeit to different degrees. Notably there were no signs of cDC, NK or IKDC activation in spleen or MLN (data not shown).


Both conventional and interferon killer dendritic cells have antigen-presenting capacity during influenza virus infection.

GeurtsvanKessel CH, Bergen IM, Muskens F, Boon L, Hoogsteden HC, Osterhaus AD, Rimmelzwaan GF, Lambrecht BN - PLoS ONE (2009)

Kinetics of increase in IKDCs, B220−NK cells, and cDCs in lung tissue after influenza virus infection.(A) Cell populations were gated as demonstrated in Figure 1. Histograms demonstrate absolute numbers of IKDCs, B220−NK cells and cDCs at different time points after infection. Bars represent mean values +/− SEM of at least 5 mice per group. CD86 (B) and MHCII (C) expression on cell populations at 4 dpi expressed as mean MFI +/− SEM, derived from at least five mice per group. Similar results were obtained from three separate experiments (D) Gene expression analysis using Aff ymetrix GeneChips. Top heat map shows NK related chemokines and growth factors. Lower map shows NK related gene products.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747012&req=5

pone-0007187-g003: Kinetics of increase in IKDCs, B220−NK cells, and cDCs in lung tissue after influenza virus infection.(A) Cell populations were gated as demonstrated in Figure 1. Histograms demonstrate absolute numbers of IKDCs, B220−NK cells and cDCs at different time points after infection. Bars represent mean values +/− SEM of at least 5 mice per group. CD86 (B) and MHCII (C) expression on cell populations at 4 dpi expressed as mean MFI +/− SEM, derived from at least five mice per group. Similar results were obtained from three separate experiments (D) Gene expression analysis using Aff ymetrix GeneChips. Top heat map shows NK related chemokines and growth factors. Lower map shows NK related gene products.
Mentions: As influenza X-31 infection is a mild infection localized in the respiratory tract, we studied the effect of infection on the number and maturation status of IKDCs in the respiratory tract (lung, bronchoalveolar compartment (BALf), mediastinal LN (MLN) and the spleen), using the multi-parameter gating strategy as above. A kinetic analysis at various days post infection (dpi) revealed that IKDCs, B220−NK cells and cDCs accumulated in the lungs with different kinetics and to different extents; IKDCs and cDCs peaking at 7dpi whereas NK cells were increased from day 1 to 7 post infection compared with mock infected mice (data shown for digested lung tissue). For clarity reasons we lumped CD11b+ and CD11b− cDCs together, but we have recently provided detail on this [13]. We next defined the co-stimulatory molecule expression on these various populations at 4 dpi. Whereas we could find an increased number of IKDCs in all compartments (Figure 3A depicts only the digested lung samples), the increase in expression of the maturation marker CD86 (Figure 3B) and expression of MHC class II (Figure 3C) molecules was restricted to the site of primary infection being lung and BALf (figures depict lung tissue) and occurred on both IKDCs, B220−NK cells and cDCs, albeit to different degrees. Notably there were no signs of cDC, NK or IKDC activation in spleen or MLN (data not shown).

Bottom Line: Here, using a model of influenza infection, we found recruitment of both conventional B220(-) NK cells and IKDCs to the lung.In vivo, the depletion of NK1.1-positive NK cells and IKDCs reduced the expansion of viral nucleoprotein-specific CD8 T cells in the lung and spleen, but did finally not affect viral clearance from the lung.In conclusion, we found evidence for APC function of lung NK cells during influenza infection, but this is a feature not exclusive to the IKDC subset.

View Article: PubMed Central - PubMed

Affiliation: Department of Pulmonary Medicine, Erasmus University Medical Centre, Rotterdam, The Netherlands.

ABSTRACT
Natural killer cells are innate effector cells known for their potential to produce interferon-gamma and kill tumour and virus-infected cells. Recently, B220(+)CD11c(int)NK1.1(+) NK cells were found to also have antigen-presenting capacity like dendritic cells (DC), hence their name interferon-producing killer DC (IKDC). Shortly after discovery, it has already been questioned if IKDC really represent a separate subset of NK cells or merely represent a state of activation. Despite similarities with DCs, in vivo evidence that they behave as bona fide APCs is lacking. Here, using a model of influenza infection, we found recruitment of both conventional B220(-) NK cells and IKDCs to the lung. To study antigen-presenting capacity of NK cell subsets and compare it to cDCs, all cell subsets were sorted from lungs of infected mice and co-cultured ex vivo with antigen specific T cells. Both IKDCs and conventional NK cells as well as cDCs presented virus-encoded antigen to CD8 T cells, whereas only cDCs presented to CD4 T cells. The absence of CD4 responses was predominantly due to a deficiency in MHCII processing, as preprocessed peptide antigen was presented equally well by cDCs and IKDCs. In vivo, the depletion of NK1.1-positive NK cells and IKDCs reduced the expansion of viral nucleoprotein-specific CD8 T cells in the lung and spleen, but did finally not affect viral clearance from the lung. In conclusion, we found evidence for APC function of lung NK cells during influenza infection, but this is a feature not exclusive to the IKDC subset.

Show MeSH
Related in: MedlinePlus