Bactericidal IL-12+ Mφ generation in sub-acutely burned mice infected with MRSA after treatment with CCL1 antisense oligodeoxynucleotides (ODN) (INC7P.415)

Abstract

Abstract Sub-acutely burned mice are shown to be carriers of M2bMφ, these cells are characterized as inhibitor cells for Mφ conversion from resident Mφ to M1Mφ. CCL1 released from M2bMφ has been identified as an essential chemokine for the maintenance of M2bMφ properties, and M2bMφ derived from sub-acutely burned mice have reverted to resident Mφ after cultivation with CCL1 antisense ODN. In this study, we tried to determine the effect of CCL1 antisense ODN on M1Mφ generation in sub-acutely burned mice infected with MRSA. Two weeks after burn injury, the mice were infected i.v. with 105 CFU/mouse of MRSA, and then, treated with the ODN (s.c., twice a day, 10 μg/mouse). Two days after the infection, F4/80+ cells were isolated from the peritoneal cavities of the mice and assayed for IL-12+ cells. Also, the killing activity of these cells against MRSA was tested in vitro. In the results, a majority of Mφ from normal mice infected with MRSA were shown to be IL-12+ cells (>82%), while 10% or less of Mφ from burn mice infected with the pathogen were IL-12+ cells. However, a majority of Mφ isolated from burn mice infected with MRSA and treated with the ODN were shown to be IL-12+ cells. A majority of Mφ from burn mice infected with MRSA were not bactericidal, while Mφ preparations from the same mice additionally treated with the ODN were bactericidal. These results indicate that M1Mφ are induced after treatment with CCL1 antisense ODN in sub-acutely burned mice infected with MRSA.