Calpains promote neutrophil recruitment and bacterial clearance in an acute bacterial peritonitis model

Kumar, Vijay, Everingham, Stephanie, Hall, Christine, Greer, Peter A. and Craig, Andrew W. B. (2014) Calpains promote neutrophil recruitment and bacterial clearance in an acute bacterial peritonitis model. European Journal of Immunology, 44 3: 831-841. doi:10.1002/eji.201343757


Author Kumar, Vijay
Everingham, Stephanie
Hall, Christine
Greer, Peter A.
Craig, Andrew W. B.
Title Calpains promote neutrophil recruitment and bacterial clearance in an acute bacterial peritonitis model
Journal name European Journal of Immunology   Check publisher's open access policy
ISSN 1521-4141
0014-2980
Publication date 2014-03-01
Year available 2013
Sub-type Article (original research)
DOI 10.1002/eji.201343757
Open Access Status Not yet assessed
Volume 44
Issue 3
Start page 831
End page 841
Total pages 11
Place of publication Weinheim, Germany
Publisher Wiley - V C H Verlag GmbH & Co. KGaA
Language eng
Abstract Activation of the innate immune system is critical for clearance of bacterial pathogens to limit systemic infections and host tissue damage. Here, we report a key role for calpain proteases in bacterial clearance in mice with acute peritonitis. Using transgenic mice expressing Cre recombinase primarily in innate immune cells (fes-Cre), we generated conditional capns1 knockout mice. Consistent with capns1 being essential for stability and function of the ubiquitous calpains (calpain-1, calpain-2), peritoneal cells from these mice had reduced levels of calpain-2/capns1, and reduced proteolysis of their substrate selenoprotein K. Using an acute bacterial peritonitis model, we observed impaired bacterial killing within the peritoneum and development of bacteremia in calpain knockout mice. These defects correlated with significant reductions in IL-1α release, neutrophil recruitment, and generation of reactive oxygen species in calpain knockout mice with acute bacterial peritonitis. Peritoneal macrophages from calpain knockout mice infected with enterobacteria ex vivo, were competent in phagocytosis of bacteria, but showed impaired clearance of intracellular bacteria compared with control macrophages. Together, these results implicate calpains as key mediators of effective innate immune responses to acute bacterial infections, to prevent systemic dissemination of bacteria that can lead to sepsis.
Keyword Bacterial infection
Calpains
Neutrophils
Phagocytosis
Reactive oxygen species
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID MOP82882
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Child Health Research Centre Publications
 
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