Combined radiation and thermal injury induces a non-suppressive myeloid CD11b+ Gr1+ cell population (P4025)

Abstract

Abstract Increasing sophistication of terrorist attacks and recent nuclear energy crises have amplified the interest in the immunobiology of combined radiation and burn injury (RCI). Burn is associated with immunosuppression and increased mortality with lower doses of ionizing radiation. Following trauma, putative myeloid derived suppressor cells (MDSCs; CD11b+Gr1+) have been described. We hypothesized that RCI-MDSCs display a suppressive phenotype and RCI will result in increased susceptibility to bacterial infection. C57BL/6 female mice underwent either a 20% total body surface area full thickness contact burn or sham procedure. All mice then received a single whole body dose of 5Gy γ-radiation. Mice were infected 14 days post injury with Pseudomonas aeruginosa intratracheally. Immune cells underwent apoptosis following RCI and infection, with CD11b+Gr1(Ly6C)+ cells being the predominant surviving cell type, which we isolated and cocultured 1:1 with untouched T cells. Surprisingly, T cells incubated with CD11b+Gr1(Ly6C)+ cells from RCI mice displayed greater proliferation, increased IFN-γ and decreased IL-10 production compared to MDSC from radiation-only mice. RCI mice were able to clear the P. aeruginosa infection significantly better than radiation-only mice. These data suggest that while RCI depletes immune cells, resistant CD11b+Gr1(Ly6C)+ cells represent a target population for modulation of bacterial clearance after injury.