NK and NKT Cell Depletion Alters the Outcome of Experimental Pneumococcal Pneumonia: Relationship with Regulation of Interferon-γ Production

Background. Natural killer (NK) and natural killer T (NKT) cells contribute to the innate host defense but their role in bacterial sepsis remains controversial. Methods. C57BL/6 mice were infected intratracheally with 5 × 105 cfu of Streptococcus pneumoniae. Animals were divided into sham group (Sha...

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Main Authors: Eirini Christaki, Evdoxia Diza, Evangelos J. Giamarellos-Bourboulis, Nikoletta Papadopoulou, Aikaterini Pistiki, Dionysia-Irini Droggiti, Marianna Georgitsi, Alzbeta Machova, Dimitra Lambrelli, Nicolaos Malisiovas, Pavlos Nikolaidis, Steven M. Opal
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2015/532717
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author Eirini Christaki
Evdoxia Diza
Evangelos J. Giamarellos-Bourboulis
Nikoletta Papadopoulou
Aikaterini Pistiki
Dionysia-Irini Droggiti
Marianna Georgitsi
Alzbeta Machova
Dimitra Lambrelli
Nicolaos Malisiovas
Pavlos Nikolaidis
Steven M. Opal
author_facet Eirini Christaki
Evdoxia Diza
Evangelos J. Giamarellos-Bourboulis
Nikoletta Papadopoulou
Aikaterini Pistiki
Dionysia-Irini Droggiti
Marianna Georgitsi
Alzbeta Machova
Dimitra Lambrelli
Nicolaos Malisiovas
Pavlos Nikolaidis
Steven M. Opal
author_sort Eirini Christaki
collection DOAJ
description Background. Natural killer (NK) and natural killer T (NKT) cells contribute to the innate host defense but their role in bacterial sepsis remains controversial. Methods. C57BL/6 mice were infected intratracheally with 5 × 105 cfu of Streptococcus pneumoniae. Animals were divided into sham group (Sham); pretreated with isotype control antibody (CON) group; pretreated with anti-asialo GM1 antibody (NKd) group; and pretreated with anti-CD1d monoclonal antibody (NKTd) group before bacterial challenge. Serum and tissue samples were analyzed for bacterial load, cytokine levels, splenocyte apoptosis rates, and cell characteristics by flow cytometry. Splenocyte miRNA expression was also analyzed and survival was assessed. Results. NK cell depletion prolonged survival. Upon inhibition of NKT cell activation, spleen NK (CD3−/NK1.1+) cells increased compared to all other groups. Inhibition of NKT cell activation led to higher bacterial loads and increased levels of serum and splenocyte IFN-γ. Splenocyte miRNA analysis showed that miR-200c and miR-29a were downregulated, while miR-125a-5p was upregulated, in anti-CD1d treated animals. These changes were moderate after NK cell depletion. Conclusions. NK cells appear to contribute to mortality in pneumococcal pneumonia. Inhibition of NKT cell activation resulted in an increase in spleen NK (CD3−/NK1.1+) cells and a higher IFN-γ production, while altering splenocyte miRNA expression.
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spelling doaj-art-3f039133e0b7470eb0df7060055d4e4e2025-08-20T02:08:07ZengWileyJournal of Immunology Research2314-88612314-71562015-01-01201510.1155/2015/532717532717NK and NKT Cell Depletion Alters the Outcome of Experimental Pneumococcal Pneumonia: Relationship with Regulation of Interferon-γ ProductionEirini Christaki0Evdoxia Diza1Evangelos J. Giamarellos-Bourboulis2Nikoletta Papadopoulou3Aikaterini Pistiki4Dionysia-Irini Droggiti5Marianna Georgitsi6Alzbeta Machova7Dimitra Lambrelli8Nicolaos Malisiovas9Pavlos Nikolaidis10Steven M. Opal11First Department of Medicine, AHEPA University Hospital, Thessaloniki, GreeceDepartment of Microbiology, Aristotle University of Thessaloniki Medical School, Thessaloniki, Greece4th Department of Internal Medicine, Medical School, University of Athens, Athens, GreeceInstitute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany4th Department of Internal Medicine, Medical School, University of Athens, Athens, Greece4th Department of Internal Medicine, Medical School, University of Athens, Athens, Greece4th Department of Internal Medicine, Medical School, University of Athens, Athens, GreeceInstitute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, GermanyDepartment of Economics, University of Macedonia, Thessaloniki, GreeceDepartment of Microbiology, Aristotle University of Thessaloniki Medical School, Thessaloniki, GreeceFirst Department of Medicine, AHEPA University Hospital, Thessaloniki, GreeceInfectious Diseases Division, Alpert Medical School of Brown University, Providence, RI, USABackground. Natural killer (NK) and natural killer T (NKT) cells contribute to the innate host defense but their role in bacterial sepsis remains controversial. Methods. C57BL/6 mice were infected intratracheally with 5 × 105 cfu of Streptococcus pneumoniae. Animals were divided into sham group (Sham); pretreated with isotype control antibody (CON) group; pretreated with anti-asialo GM1 antibody (NKd) group; and pretreated with anti-CD1d monoclonal antibody (NKTd) group before bacterial challenge. Serum and tissue samples were analyzed for bacterial load, cytokine levels, splenocyte apoptosis rates, and cell characteristics by flow cytometry. Splenocyte miRNA expression was also analyzed and survival was assessed. Results. NK cell depletion prolonged survival. Upon inhibition of NKT cell activation, spleen NK (CD3−/NK1.1+) cells increased compared to all other groups. Inhibition of NKT cell activation led to higher bacterial loads and increased levels of serum and splenocyte IFN-γ. Splenocyte miRNA analysis showed that miR-200c and miR-29a were downregulated, while miR-125a-5p was upregulated, in anti-CD1d treated animals. These changes were moderate after NK cell depletion. Conclusions. NK cells appear to contribute to mortality in pneumococcal pneumonia. Inhibition of NKT cell activation resulted in an increase in spleen NK (CD3−/NK1.1+) cells and a higher IFN-γ production, while altering splenocyte miRNA expression.http://dx.doi.org/10.1155/2015/532717
spellingShingle Eirini Christaki
Evdoxia Diza
Evangelos J. Giamarellos-Bourboulis
Nikoletta Papadopoulou
Aikaterini Pistiki
Dionysia-Irini Droggiti
Marianna Georgitsi
Alzbeta Machova
Dimitra Lambrelli
Nicolaos Malisiovas
Pavlos Nikolaidis
Steven M. Opal
NK and NKT Cell Depletion Alters the Outcome of Experimental Pneumococcal Pneumonia: Relationship with Regulation of Interferon-γ Production
Journal of Immunology Research
title NK and NKT Cell Depletion Alters the Outcome of Experimental Pneumococcal Pneumonia: Relationship with Regulation of Interferon-γ Production
title_full NK and NKT Cell Depletion Alters the Outcome of Experimental Pneumococcal Pneumonia: Relationship with Regulation of Interferon-γ Production
title_fullStr NK and NKT Cell Depletion Alters the Outcome of Experimental Pneumococcal Pneumonia: Relationship with Regulation of Interferon-γ Production
title_full_unstemmed NK and NKT Cell Depletion Alters the Outcome of Experimental Pneumococcal Pneumonia: Relationship with Regulation of Interferon-γ Production
title_short NK and NKT Cell Depletion Alters the Outcome of Experimental Pneumococcal Pneumonia: Relationship with Regulation of Interferon-γ Production
title_sort nk and nkt cell depletion alters the outcome of experimental pneumococcal pneumonia relationship with regulation of interferon γ production
url http://dx.doi.org/10.1155/2015/532717
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