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Updated: May 29, 2026
A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
Increased susceptibility of ST2-deficient mice to polymicrobial sepsis is associated with an impaired bactericidal
Julliette M Buckley1, Jing Hua Liu, Chong Hui Li
1Department of Academic Surgery, University College Cork/National University of Ireland, Cork University Hospital, Cork, Ireland.
Abstract:
ST2, a member of the Toll/IL-1R superfamily, negatively regulates both TLR2 and TLR4 signaling. In this study, we report that ST2-deficient mice were more susceptible to polymicrobial sepsis than their wild-type littermates, with increased production of proinflammatory cytokines. Bacterial clearance from the circulation and visceral organs following polymicrobial infection was markedly impaired in ST2-deficient mice. This was associated with substantially reduced uptake, phagocytosis, and intracellular killing of both Gram-positive and Gram-negative bacteria by ST2-deficient phagocytes. Consistent with a reduced antimicrobial response, phagocytes lacking ST2 displayed a defect in bactericidal activity in response to bacterial challenges with severely impaired phagosome maturation and NOX2 function. Thus, ST2-deficient mice exhibit an increased susceptibility to polymicrobial infection with impaired bacterial clearance, which is associated with defects in phagosome maturation and NOX2-derived production of reactive oxygen species characterized in ST2-deficient phagocytes.
Insights
Mice lacking ST2 (suppression of tumorigenicity 2) showed increased susceptibility to sepsis due to impaired bacterial clearance. Their phagocytes had defects in bacterial uptake, killing, and maturation, highlighting ST2's role in the immune response.
Area of Science:
- Immunology
- Infectious Disease
Background:
- ST2, a member of the Toll/IL-1R superfamily, is known to negatively regulate Toll-like receptor (TLR) signaling.
- Understanding ST2's role in host defense against bacterial infections is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To investigate the role of ST2 in host defense against polymicrobial sepsis.
- To elucidate the mechanisms underlying impaired bacterial clearance in ST2-deficient mice.
Main Methods:
- Utilized ST2-deficient and wild-type littermate mice in a polymicrobial sepsis model.
- Assessed bacterial load in circulation and visceral organs.
- Analyzed phagocyte function, including bacterial uptake, phagocytosis, intracellular killing, phagosome maturation, and NOX2 activity.
Main Results:
- ST2-deficient mice exhibited increased susceptibility to polymicrobial sepsis compared to wild-type controls.
- Impaired bacterial clearance was observed in ST2-deficient mice, with higher bacterial loads in circulation and organs.
- ST2-deficient phagocytes showed reduced uptake, phagocytosis, and intracellular killing of bacteria.
- Defects in phagosome maturation and NOX2 function were identified in ST2-deficient phagocytes, leading to reduced bactericidal activity.
Conclusions:
- ST2 plays a critical role in host defense against polymicrobial sepsis by promoting bacterial clearance.
- Deficiency in ST2 impairs phagocyte antimicrobial functions, including phagosome maturation and reactive oxygen species production via NOX2.
- Targeting ST2 may offer a therapeutic avenue for enhancing host defense in sepsis and other bacterial infections.
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Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...