title: NK and NKT Cell Depletion Alters the Outcome of Experimental Pneumococcal Pneumonia: Relationship with Regulation of Interferon-γ Production.
abstract: 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 × 10(5) 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.
authors.affiliation: First Department of Medicine, AHEPA University Hospital, Thessaloniki, Greece ; Infectious Diseases Division, Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Eirini
authors.identifier: 0000-0002-8152-6367
authors.initials: E
authors.lastname: Christaki
authors.affiliation: Department of Microbiology, Aristotle University of Thessaloniki Medical School, Thessaloniki, Greece.
authors.forename: Evdoxia
authors.initials: E
authors.lastname: Diza
authors.affiliation: 4th Department of Internal Medicine, Medical School, University of Athens, Athens, Greece.
authors.forename: Evangelos J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Papadopoulou
authors.affiliation: 4th Department of Internal Medicine, Medical School, University of Athens, Athens, Greece.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Pistiki
authors.affiliation: 4th Department of Internal Medicine, Medical School, University of Athens, Athens, Greece.
authors.forename: Dionysia-Irini
authors.initials: DI
authors.lastname: Droggiti
authors.affiliation: 4th Department of Internal Medicine, Medical School, University of Athens, Athens, Greece.
authors.forename: Marianna
authors.initials: M
authors.lastname: Georgitsi
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
authors.forename: Alzbeta
authors.initials: A
authors.lastname: Machova
authors.affiliation: Department of Economics, University of Macedonia, Thessaloniki, Greece.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Lambrelli
authors.affiliation: Department of Microbiology, Aristotle University of Thessaloniki Medical School, Thessaloniki, Greece.
authors.forename: Nicolaos
authors.initials: N
authors.lastname: Malisiovas
authors.affiliation: First Department of Medicine, AHEPA University Hospital, Thessaloniki, Greece.
authors.forename: Pavlos
authors.initials: P
authors.lastname: Nikolaidis
authors.affiliation: Infectious Diseases Division, Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Opal
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000096:biosynthesis; D053208:Kaplan-Meier Estimate; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008212:Lymphocyte Depletion; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D007371:Interferon-gamma