Related Experiment Video
Updated: Mar 15, 2026
A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
Macrophage polarization and MRSA infection in burned mice
Tomoki Nishiguchi1, Ichiaki Ito1, Jong O Lee2
1Division of Infectious Diseases, Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX, USA.
Abstract:
Mortality associated with Staphylococcus aureus infection remains high during the sub-acute phase of burn injury. In this study, we aimed to improve antibacterial resistance of sub-acutely burned mice through macrophage polarization. Sepsis did not develop in mice at the sub-acute phase of 5% total body surface area (TBSA) burn after being infected with methicillin-resistant S. aureus (MRSA), and M1 macrophages (interleukin (IL)-10-IL-12+ inducible nitric oxide synthase+ Mφ) were isolated from these mice. In contrast, predominantly M2b macrophages (C-C motif chemokine ligand 1 (CCL1)+IL-10+IL-12- Mφ) were isolated from mice with >15% TBSA burn, and all of these mice died after the same MRSA infection. Comparing NOD scid gamma mice inoculated with Mφ with 25% TBSA burns, all mice treated with CCL1 antisense oligodeoxynucleotide (ODN) survived after MRSA infection, whereas all untreated mice given the same infection died within 4 days. CCL1 antisense ODN has been characterized as a specific polarizer of M2bMφ. M1Mφ were isolated from MRSA-infected mice with 25% TBSA burn after treatment with CCL1 antisense ODN, and these mice were shown to be resistant against a lethal dose of MRSA infection. M1Mφ were also isolated from 25% TBSA-burned mice infected with MRSA when the ODN was administered therapeutically, and subsequent sepsis was effectively controlled in these mice. These results indicate that the M2bMφ polarizer is beneficial for controlling MRSA infection in mice at the sub-acute phase of severe burn injury.
Insights
Targeting macrophage polarization can enhance antibacterial resistance in severe burn injuries. This study shows that M1 macrophages protect against Staphylococcus aureus, while M2b macrophages are linked to mortality, offering a potential therapeutic strategy.
Area of Science:
- Immunology
- Wound Healing
- Infectious Diseases
Background:
- High mortality rates persist during the sub-acute phase of burn injuries due to Staphylococcus aureus infections.
- Macrophage polarization plays a critical role in modulating the immune response to infection and injury.
- Distinct macrophage phenotypes (M1 and M2b) are associated with different outcomes in burn-infected mice.
Purpose of the Study:
- To investigate the potential of macrophage polarization for improving antibacterial resistance in sub-acutely burned mice.
- To explore the role of M1 and M2b macrophages in the context of methicillin-resistant S. aureus (MRSA) infection following burn injury.
- To evaluate the therapeutic efficacy of targeting M2b macrophages to control MRSA infection in severe burn models.
Main Methods:
- Comparison of macrophage populations (M1 vs. M2b) in mice with varying total body surface area (TBSA) burns infected with MRSA.
- Administration of C-C motif chemokine ligand 1 (CCL1) antisense oligodeoxynucleotide (ODN) to polarize macrophages and assess its impact on survival.
- Analysis of macrophage phenotypes and MRSA infection control in mice treated with CCL1 antisense ODN, including therapeutic administration.
Main Results:
- Mice with smaller burns (5% TBSA) showed M1 macrophage presence and survived MRSA infection, while those with larger burns (>15% TBSA) exhibited M2b macrophages and succumbed to infection.
- Treatment with CCL1 antisense ODN, a specific M2b macrophage polarizer, significantly improved survival rates in mice with 25% TBSA burns infected with MRSA.
- CCL1 antisense ODN treatment led to the isolation of protective M1 macrophages and effectively controlled sepsis in therapeutically treated mice.
Conclusions:
- M2b macrophages are associated with mortality in MRSA-infected burn patients during the sub-acute phase.
- Targeting M2b macrophages with specific polarizers like CCL1 antisense ODN can enhance resistance to MRSA infection.
- Macrophage polarization represents a promising therapeutic strategy for managing severe burn injuries complicated by MRSA sepsis.
