CCL1 released from M2b macrophages is essentially required for the maintenance of their properties

Patients with 10-30 days postburn injury are greatly susceptible to infections. M1M phi (IL-10(-)IL-12(+)M phi) are essential cells in host antibacterial innate immunity against MRSA infections. However, these effector cells are not easily generated in hosts who are carriers of M2bM phi (IL-12(-)IL-10(+)CCL1(+)LIGHT(+)M phi). M2bM phi are inhibitory on M1M phi generation. In this study, the antibacterial resistance of mice, 10-30 days postburn injury against MRSA infection, was improved by the modulation of M2bM phi activities. Unburned mice inoculated with M phi preparations from mice, 10-30 days after burn injury, were susceptible to MRSA infection, whereas unburned mice, inoculated with M phi preparations from the same mice that were previously treated with CCL1 antisense ODN, were resistant to the infection. M2bM phi, isolated from Day 15 burn mice, lost their M2bM phi properties 3 days after cultivation under frequent medium changes, whereas their M2bM phi properties remained in the same cultures supplemented with rCCL1. In cultures, M phi preparations from Day 15 burn mice treated with CCL1 antisense ODN did not produce CCL1 and did convert to M1M phi after heat-killed MRSA stimulation. Also, Day 15 burn mice treated with the ODN became resistant against MRSA infection. These results indicate that CCL1 released from M2bM phi is essentially required for the maintenance of their properties. The increased susceptibility of mice, 10-30 days after burn injury to MRSA infection, may be controlled through the intervention of CCL1 production by M2bM phi appearing in association with severe burn injuries. J. Leukoc. Biol. 92: 859-867; 2012.