Enterococcus faecalis translocation in mice with severe burn injury: a pathogenic role of CCL2 and alternatively activated macrophages (M2aMφ and M2cMφ)

Here, we investigated a role of CCL2 on the increased susceptibility of severely burned mice to Enterococcus faecalis translocation. After inoculation of M phi from MLM phi of normal mice, 80% of the SCIDbgMN mice orally infected with the lethal dose of E. faecalis survived, and all mice inoculated with MLM phi from thermally injured mice died. At this time, SCIDbgMN mice inoculated with MLM phi from thermally injured CCL2(-/-) mice were shown to be resistant (90% survival). M1M phi were not induced by E. faecalis antigen in cultures of MLM phi from thermally injured wild-type mice, and MLM phi from thermally injured CCL2(-/-) mice converted to M1M phi after the antigen stimulation. MLM phi from wild-type mice 2 days postburn injury possessed M2a- and M2cM phi properties, and those from mice 7-21 days postburn injury carried M2bM phi properties. However, MLM phi from thermally injured CCL2(-/-) mice did not show any typical properties for M2a- or M2cM phi. CCL17 and CXCL13 (biomarkers for M2a- and M2cM phi), but not CCL1 (a biomarker of M2bM phi), were produced by MLM phi from thermally injured CCL2(-/-) mice treated with rCCL2. These results indicate that CCL2 converts resident MLM phi to M2a- and M2cM phi, detected early after burn injury, and decreases host antibacterial innate immunity against sepsis stemming from oral E. faecalis infection. J. Leukoc. Biol. 86: 999-1005; 2009.