Severe burn injury leads to spontaneous generation of Th17 CD4+ T cells in wound draining lymph nodes (42.18)

Abstract

Abstract Severe burn injury leads to early and prolonged immune dysfunction resulting in a reduced resistance to bacterial infection. In a model of burn injury, we have previously shown that burn mice challenged with Pseudomonas aeruginosa develop systemic infection and have high mortality rates whereas sham mice do not. Wound tissue TGF-β levels and serum IL-6 levels are elevated in the infected burn (IL-6: 32.68 +/- 9.53 pg/mL, n=4) compared to infected sham (2.87 +/- 1.43, n=3) mice. IFN-γ levels are similar between the groups. Since TGF-β and IL-6 are key for differentiation of naïve CD4+ T cells into the Th17 phenotype, we hypothesized that Th17 T cells are generated following burn injury. Female C57BL/6 mice were anesthetized and subjected to 20% full thickness contact burn or sham procedure. After 3, 7 or 14 days, CD4+ T cells selected from wound-draining lymph nodes were in vitro stimulated with mitogen. Flow cytometry was used to identify intracellular IL-17 in CD3+ CD4+ T cells. At all time points there was a statistically significant burn-dependent increase in both percentage of CD4+ T cells that were Th17 cells and absolute Th17 cell number (e.g. Day 3, 7384 +/- 1370 cells, n=3) compared to sham (1604 +/- 499, n=5). While burn injury spontaneously induces Th17 cells, known to recruit neutrophils, this does not protect against subsequent P. aeruginosa challenge. This may provide a novel mechanism for post-burn immunosuppression.