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Updated: Jun 30, 2026
A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
Pretreatment with the Gram-positive bacterial cell wall molecule peptidoglycan improves bacterial clearance and
E D Murphey1, Geping Fang, Edward R Sherwood
1Department of Anesthesiology, Shriners Burns Institute, University of Texas Medical Branch, Galveston, TX, USA. edmurphe@utmb.edu
Objective:
To determine whether tolerance and enhancement of innate immune function can be induced by the Gram-positive cell wall component peptidoglycan.
Design:
Controlled, in vivo laboratory study.
Subjects:
Male mice, 8-12 wks (C57BL6/J; C3H/HeJ; B6.129-Tlr2/J).
Interventions:
Mice were given intraperitoneal injections of 1 mg peptidoglycan on two consecutive days. Mice were then challenged with an intravenous injection of live Staphylococcus aureus (1 x 10 colony-forming units) 2 days after the second pretreatment.
Measurements And Main Results:
Mice pretreated with peptidoglycan had diminished plasma concentrations of tumor necrosis factor-alpha and interferon-gamma in response to the bacterial challenge when compared with untreated controls. Plasma interleukin-10 after bacterial challenge was higher in peptidoglycan-pretreated mice than in controls. Clearance of bacteria after the staphylococcal challenge was improved in mice pretreated with peptidoglycan, and mortality in response to a subsequent Staphylococcus challenge was significantly attenuated. Peptidoglycan pretreatment of mice lacking intact toll-like receptor-4 signaling (C3H/HeJ) or toll-like receptor-2 signaling (toll-like receptor-2 knockouts) had similar effects on plasma cytokine balance, bacterial clearance, and mortality.
Conclusions:
Exposure to peptidoglycan significantly attenuated inflammation and enhanced bacterial clearance after a subsequent challenge with S. aureus. These results show that exposure to Gram-positive bacterial cell wall components can induce tolerance and enhance innate immune function and neither toll-like receptor-2 nor toll-like receptor-4 are necessary for this phenomenon. Further, although the altered cytokine balance is similar to that seen in septic patients, induced tolerance differs importantly from the clinical scenario of sepsis in that bacterial clearance and survival are improved compared with normal control animals.
Insights
Pretreating mice with peptidoglycan, a Gram-positive cell wall component, reduced inflammation and improved bacterial clearance against Staphylococcus aureus. This innate immune enhancement occurred independently of toll-like receptor-2 and toll-like receptor-4 signaling.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Gram-positive bacteria possess cell wall components like peptidoglycan.
- Innate immune responses are crucial for host defense against bacterial infections.
- Toll-like receptors (TLRs) play a significant role in recognizing microbial components and initiating immune responses.
Purpose of the Study:
- To investigate if peptidoglycan can induce tolerance and enhance innate immune function.
- To determine the role of TLR-2 and TLR-4 in peptidoglycan-mediated immune modulation.
Main Methods:
- A controlled in vivo laboratory study using male mice (C57BL6/J, C3H/HeJ, B6.129-Tlr2/J).
- Mice received intraperitoneal injections of peptidoglycan on two consecutive days.
- Mice were subsequently challenged with live Staphylococcus aureus to assess immune responses.
Main Results:
- Peptidoglycan pretreatment significantly reduced pro-inflammatory cytokines (TNF-α, IFN-γ) and increased anti-inflammatory cytokine (IL-10) after S. aureus challenge.
- Enhanced bacterial clearance and significantly attenuated mortality were observed in peptidoglycan-pretreated mice.
- These effects were consistent in mice lacking functional TLR-2 or TLR-4 signaling.
Conclusions:
- Exposure to peptidoglycan induces immune tolerance and enhances innate immunity against S. aureus.
- Neither TLR-2 nor TLR-4 signaling is essential for peptidoglycan-induced immune tolerance and enhanced bacterial clearance.
- Induced tolerance differs from clinical sepsis, as it improves bacterial clearance and survival.
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