Enterococcus faecalis translocation in mice with severe burn injury: a pathogenic role of CCL2 and alternatively activated macrophages (M2aMphi and M2cMphi)
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Published on: February 19, 2013
Kenji Shigematsu1, Akira Asai, Makiko Kobayashi
1Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 77555-0435, USA.
Abstract:
Here, we investigated a role of CCL2 on the increased susceptibility of severely burned mice to Enterococcus faecalis translocation. After inoculation of Mphi from MLMphi of normal mice, 80% of the SCIDbgMN mice orally infected with the lethal dose of E. faecalis survived, and all mice inoculated with MLMphi from thermally injured mice died. At this time, SCIDbgMN mice inoculated with MLMphi from thermally injured CCL2(-/-) mice were shown to be resistant (90% survival). M1Mphi were not induced by E. faecalis antigen in cultures of MLMphi from thermally injured wild-type mice, and MLMphi from thermally injured CCL2(-/-) mice converted to M1Mphi after the antigen stimulation. MLMphi from wild-type mice 2 days postburn injury possessed M2a- and M2cMphi properties, and those from mice 7-21 days postburn injury carried M2bMphi properties. However, MLMphi from thermally injured CCL2(-/-) mice did not show any typical properties for M2a- or M2cMphi. CCL17 and CXCL13 (biomarkers for M2a- and M2cMphi), but not CCL1 (a biomarker of M2bMphi), were produced by MLMphi from thermally injured CCL2(-/-) mice treated with rCCL2. These results indicate that CCL2 converts resident MLMphi to M2a- and M2cMphi, detected early after burn injury, and decreases host antibacterial innate immunity against sepsis stemming from oral E. faecalis infection.
Insights
Chemokine (C-C motif) ligand 2 (CCL2) converts macrophages to M2 phenotypes after severe burns, increasing susceptibility to Enterococcus faecalis infection. Blocking CCL2 enhances host immunity against bacterial sepsis.
Area of Science:
- Immunology
- Microbiology
- Wound Healing
Background:
- Severe burns compromise innate immunity, increasing susceptibility to opportunistic infections like Enterococcus faecalis.
- Macrophage (Mphi) polarization is crucial in regulating immune responses post-burn injury.
- The role of CCL2 in modulating Mphi function and host defense following thermal injury remains unclear.
Purpose of the Study:
- To investigate the role of CCL2 in modulating macrophage polarization after severe burn injury.
- To determine the impact of CCL2-induced macrophage changes on susceptibility to Enterococcus faecalis infection.
- To elucidate the mechanisms by which CCL2 affects innate immunity post-burn.
Main Methods:
- Utilized a murine model of severe burn injury and Enterococcus faecalis oral infection.
- Assessed survival rates in SCIDbgMN mice inoculated with macrophages from wild-type and CCL2-deficient burned mice.
- Analyzed macrophage phenotypes (M1, M2a, M2c, M2b) and biomarker expression (CCL17, CXCL13, CCL1) using cell cultures and molecular techniques.
Main Results:
- Macrophages (MLMphi) from thermally injured wild-type mice exhibited M2 phenotypes (M2a, M2c, M2b) and failed to induce M1 polarization in response to E. faecalis antigen.
- SCIDbgMN mice receiving MLMphi from burned wild-type mice showed high mortality, while those receiving MLMphi from burned CCL2(-/-) mice exhibited 90% survival.
- MLMphi from burned CCL2(-/-) mice converted to M1 phenotype upon antigen stimulation and lacked M2a/M2c properties unless treated with recombinant CCL2 (rCCL2), which induced CCL17 and CXCL13 expression.
Conclusions:
- CCL2 converts resident macrophages to M2a and M2c phenotypes early after burn injury.
- This CCL2-mediated M2 polarization impairs host antibacterial innate immunity, increasing susceptibility to E. faecalis sepsis.
- Targeting CCL2 may represent a therapeutic strategy to restore innate immunity and improve outcomes in burn patients.
