Published in:
Open Access
01-12-2014 | Research article
Limited role for ASC and NLRP3 during in vivo Salmonella Typhimurium infection
Authors:
Hanna K De Jong, Gavin CKW Koh, Miriam HP van Lieshout, Joris JTH Roelofs, Jaap T van Dissel, Tom van der Poll, W Joost Wiersinga
Published in:
BMC Immunology
|
Issue 1/2014
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Abstract
Background
The inflammasome is an intracellular protein complex triggered by exposure to intracellular pathogens, its components or other endogenous proteins. It leads to the activation of and subsequent release of proinflammatory cytokines such as IL-1β and IL-18. S. Typhimurium is a Gram-negative intracellular bacterium, which is known to trigger inflammasome assembly via recognition by the cytosolic receptors, NLRP3 and NLRC4 (which act via the adaptor protein, ASC) to induce cell death and cytokine release. We sought to characterize the role of ASC and NLRP3 in two different murine models (typhoid and colitis) of systemic Salmonella infection.
Results
Release of the inflammasome cytokine IL-18 was hampered in Asc
−/−
but not Nlrp3
−/−
mice (background C57BL/6) during S. Typhimurium infection. Unexpectedly, neither ASC nor NLRP3 played a significant role in host defense against S. Typhimurium infection, as reflected by equal bacterial counts in WT, Asc
−/−
and Nlrp3
−/−
mice at all time points, in both the typhoid and colitis models. Proinflammatory cytokine levels (TNF-α, IL-6) and the extent of hepatic and splenic pathology did not differ between groups in the typhoid model. In the colitis model small differences were seen with regard to splenic and hepatic inflammation, although this was IL-18 independent.
Conclusions
IL-18 release was reduced in Asc
−/−
but not Nlrp3
−/−
mice during S. Typhimurium infection. Despite this reduction, bacterial counts, cytokine levels and histological inflammation did not differ between wild-type and knockout mice in either model. Our results reveal a limited role for ASC and NLRP3 during in vivo S. Typhimurium infection despite its role in cytokine maturation.