The Natural Cytotoxicity Receptor 1 Contribution to Early Clearance of Streptococcus pneumoniae and to Natural Killer-Macrophage Cross Talk

The Shraga Segal Department of Microbiology and Immunology and the National Institute for Biotechnology in the Negev, Ben Gurion University of the Negev, Beer Sheva, Israel.
PLoS ONE (Impact Factor: 3.23). 08/2011; 6(8):e23472. DOI: 10.1371/journal.pone.0023472
Source: PubMed


Natural killer (NK) cells serve as a crucial first line of defense against tumors, viral and bacterial infections. We studied the involvement of a principal activating natural killer cell receptor, natural cytotoxicity receptor 1 (NCR1), in the innate immune response to S. pneumoniae infection. Our results demonstrate that the presence of the NCR1 receptor is imperative for the early clearance of S. pneumoniae. We tied the ends in vivo by showing that deficiency in NCR1 resulted in reduced lung NK cell activation and lung IFNγ production at the early stages of S. pneumoniae infection. NCR1 did not mediate direct recognition of S. pneumoniae. Therefore, we studied the involvement of lung macrophages and dendritic cells (DC) as the mediators of NK-expressed NCR1 involvement in response to S. pneumoniae. In vitro, wild type BM-derived macrophages and DC expressed ligands to NCR1 and co-incubation of S. pneumoniae-infected macrophages/DC with NCR1-deficient NK cells resulted in significantly lesser IFNγ levels compared to NCR1-expressing NK cells. In vivo, ablation of lung macrophages and DC was detrimental to the early clearance of S. pneumoniae. NCR1-expressing mice had more potent alveolar macrophages as compared to NCR1-deficient mice. This result correlated with the higher fraction of NCR1-ligand(high) lung macrophages, in NCR1-expressing mice, that had better phagocytic activity compared to NCR1-ligand(dull) macrophages. Overall, our results point to the essential contribution of NK-expressed NCR1 in early response to S. pneumoniae infection and to NCR1-mediated interaction of NK and S. pneumoniae infected-macrophages and -DC.

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    • "In contrast, NKp46-expressing wild type mice appear to be endowed with potent alveolar macrophage responses as compared to NCR1-deficient mice. This result correlates with the higher fraction of NKp46 ligand on lung macrophages in NCR1-expressing mice that are also equipped with better phagocytic activity compared to that of macrophages with lower or negative surface levels of NKp46 ligands (Elhaik-Goldman et al., 2011). "
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    Frontiers in Immunology 03/2013; 4(69):69. DOI:10.3389/fimmu.2013.00069
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    • "In addition, other NK activating receptor may also contribute to lysis of NK cells during the interaction with macrophages. NCR1 (murine NKp46) was reported to be important for NK cell activation during the interaction with S. pneumoniae-infected BMMQ [34]. In human, IFN-γ production of NK cell was shown require the interaction of DNAM-1 and 2B4 with their ligands on macrophage exposure to LPS or bacillus Calmette–Guérin [35]. "
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    ABSTRACT: Natural killer (NK) cells and their crosstalk with other immune cells are important for innate immunity against tumor. To explore the role of the interaction between NK cells and macrophages in the regulation of anti-tumor activities of NK cells, we here demonstrate that poly I:C-treated macrophages increased NK cell-mediated cytotoxicity against target tumor cells in NKG2D-dependent manner. In addition, IL-15, IL-18, and IFN-β secreted by poly I:C-treated macrophages are also involved in NKG2D expression and NK cell activation. Interestingly, the increase in expression of NKG2D ligands on macrophages induced a highly NK cell-mediated cytotoxicity against tumor cells, but not against macrophages themselves. Notably, a high expression level of Qa-1, a NKG2A ligand, on macrophages may contribute to such protection of macrophages from NK cell-mediated killing. Furthermore, Qa-1 or NKG2A knockdown and Qa-1 antibody blockade caused the macrophages to be sensitive to NK cytolysis. These results suggested that macrophages may activate NK cells to attack tumor by NKG2D recognition whereas macrophages protect themselves from NK lysis via preferential expression of Qa-1.
    PLoS ONE 05/2012; 7(5):e36928. DOI:10.1371/journal.pone.0036928 · 3.23 Impact Factor
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    • "Several groups have shown an upregulation of CD69 at the NK cell surface, the production of IFN-γ and the degranulation of NK cells when monocytes/macrophages were previously stimulated by molecules like Lacto-N-fucopentaose III, poly I:C, CpG DNA, and LPS (Chace et al., 1997; Scott et al., 2004; Atochina and Harn, 2005; Basu et al., 2009; Bellora et al., 2010; Zhou et al., 2012). Infection by parasites, like P. falciparum and Leishmania (Aranha et al., 2005; Baratin et al., 2005), or viruses, like influenza A virus, Sendai virus, human cytomegalovirus (Siren et al., 2004; Romo et al., 2011), or bacteria like Salmonella, M. tuberculosis, E. faecalis, S. aureus, Lactobacillus, S. pneumonia, and B. anthracis, has the same effects (Brill et al., 2001; Haller et al., 2002; Schierloh et al., 2005; Denis et al., 2007; Newman and Riley, 2007; Lapaque et al., 2009; Takayama et al., 2010; Elhaik-Goldman et al., 2011; Klezovich-Benard et al., 2012; Souza-Fonseca-Guimaraes et al., 2012). "
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