Table of Contents Author Guidelines Submit a Manuscript
Mediators of Inflammation
Volume 2017, Article ID 4137563, 11 pages
https://doi.org/10.1155/2017/4137563
Research Article

Expression and Function of Granzymes A and B in Escherichia coli Peritonitis and Sepsis

1Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands
2Department of Immunopathology, Sanquin Research, Plesmanlaan 125, 1066 CX Amsterdam, Netherlands
3Department of Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands
4Laboratory for Experimental Oncology and Radiobiology (LEXOR), Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands
5Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands

Correspondence should be addressed to M. Isabel García-Laorden; se.oohay@lgmelahi

Received 12 February 2017; Revised 5 April 2017; Accepted 20 April 2017; Published 12 June 2017

Academic Editor: Mirella Giovarelli

Copyright © 2017 M. Isabel García-Laorden 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

Escherichia (E.) coli is the most common causative pathogen in peritonitis, the second most common cause of sepsis. Granzymes (gzms) are serine proteases traditionally implicated in cytotoxicity and, more recently, in the inflammatory response. We here sought to investigate the role of gzms in the host response to E. coli-induced peritonitis and sepsis in vivo. For this purpose, we used a murine model of E. coli intraperitoneal infection, resembling the clinical condition commonly associated with septic peritonitis by this bacterium, in wild-type and gzmA-deficient (gzmA−/−), gzmB−/−, and gzmAxB−/−mice. GzmA and gzmB were predominantly expressed by natural killer cells, and during abdominal sepsis, the percentage of these cells expressing gzms in peritoneal lavage fluid decreased, while the amount of expression in the gzm+ cells increased. Deficiency of gzmA and/or gzmB was associated with increased bacterial loads, especially in the case of gzmB at the primary site of infection at late stage sepsis. While gzm deficiency did not impact neutrophil recruitment into the abdominal cavity, it was accompanied by enhanced nucleosome release at the primary site of infection, earlier hepatic necrosis, and more renal dysfunction. These results suggest that gzms influence bacterial growth and the host inflammatory response during abdominal sepsis caused by E. coli.