title: The natural cytotoxicity receptor 1 contribution to early clearance of Streptococcus pneumoniae and to natural killer-macrophage cross talk.
abstract: 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.
authors: 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.
authors: Shirin
authors: S
authors: Elhaik-Goldman
authors: Daniel
authors: D
authors: Kafka
authors: Rami
authors: R
authors: Yossef
authors: Uzi
authors: U
authors: Hadad
authors: Moshe
authors: M
authors: Elkabets
authors: Alexandra
authors: A
authors: Vallon-Eberhard
authors: Luai
authors: L
authors: Hulihel
authors: Steffen
authors: S
authors: Jung
authors: Hormas
authors: H
authors: Ghadially
authors: Alex
authors: A
authors: Braiman
authors: Ron N
authors: RN
authors: Apte
authors: Ofer
authors: O
authors: Mandelboim
authors: Ron
authors: R
authors: Dagan
authors: Yaffa
authors: Y
authors: Mizrachi-Nebenzahl
authors: Angel
authors: A
authors: Porgador
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism*; D058491:Bacterial Load / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000276:immunology*; D016019:Survival Analysis
chemical_list: D000950:Antigens, Ly; D016207:Cytokines; D008024:Ligands; D055627:Natural Cytotoxicity Triggering Receptor 1; C118384:Ncr1 protein, mouse; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins