Burn injury induces a myeloid suppressor phenotype and susceptibility to Pseudomonas infection (129.24)

Abstract

Following severe burn injury, the immune system is dramatically altered resulting in a susceptibility to bacterial infections. Using a mouse model of burn injury and subsequent Pseudomonas aeruginosa infection, we hypothesized that 1) clearance will be decreased after burn and 2) expression of TLR2, important for P. aeruginosa clearance, and/or Gr1.1, a marker of myeloid suppressive ability, is altered by burn. Female C57BL/6 mice were subjected to a 20% full thickness contact burn or sham procedure. After one day, mice were inoculated s/c at the wound with 2 x104 CFU of P. aeruginosa. CFU were calculated for various organs after two days. Splenocytes were analyzed by FACS for CD11b, Gr1.1 and TLR2. Burn mice had significant morbidity (weight loss) and mortality versus sham. Burn mice developed a systemic infection (e.g. mean±SEM 4.4±0.6 x104 CFU/lung, n=6) while no CFU were recovered from sham (n=6). Infected burn mice had a significantly higher number and percent of CD11b+ TLR2hi splenocytes (22.6±3.5%) than the infected sham (3.4±0.4%). A higher number and percent of burn CD11b+ cells were Gr1.1+ (75.5±5.7%) compared to sham mice (43.3±1.2%). Therefore, although we observed an increase in TLR2+ myeloid cells following burn injury, the increased percentage of GR1.1+ CD11b+ myeloid suppressor cells could contribute to the development of a systemic P. aeruginosa infection after burn. Supported by NIH K08 067147.