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Journal of Immunology Research
Volume 2015, Article ID 532717, 10 pages
http://dx.doi.org/10.1155/2015/532717
Research Article

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

1First Department of Medicine, AHEPA University Hospital, Thessaloniki, Greece
2Infectious Diseases Division, Alpert Medical School of Brown University, Providence, RI, USA
3Department of Microbiology, Aristotle University of Thessaloniki Medical School, Thessaloniki, Greece
44th Department of Internal Medicine, Medical School, University of Athens, Athens, Greece
5Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany
6Department of Economics, University of Macedonia, Thessaloniki, Greece

Received 26 February 2015; Revised 29 April 2015; Accepted 3 May 2015

Academic Editor: Peirong Jiao

Copyright © 2015 Eirini Christaki et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 × 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.