Cobalt-chrome micro-particles induce a robust MyD88-independent, Caspase1-dependent type 2 immune response (P1266)

Abstract

Abstract Wear debris particles associated with prosthetic devices may cause inflammation. In our previous study, we demonstrated that micrometer size Titanium particles induce a robust innate and adaptive type 2 in vivo immune response. In this study, we examined the size and mechanisms of particle induced type 2 inflammation, using Cobalt Chrome (COCR). Intra-peritoneal injection of 50 mg COCR (>10micron) still induced a type 2 innate response with marked increases in M2 macrophages, neutrophil and eosinophils independent of MYD88/TRIFF signaling pathways. We observed a marked decrease in the infiltration of neutrophil and M2 macrophages in Caspase-1-/- mice compared to wild type mice suggesting an essential role for inflammasome-mediated pathways. Intra peritoneal injection with smaller size COCR particles (<10micron) showed less infiltration of Th2 innate cells compared to the large size COCR particle (>10micron). We also examined the adjuvant nature of COCR particles by immunizing mice with COCR microparticles + OVA peptide after transfer of CFSE-labeled OVA specific DO11.10 CD4+ T cells. After 7 days marked increases in OVA-specific T cell proliferation and IL-4 production was observed compared to mice immunized with OVA alone. These studies indicate that induction of the type 2 immune response is triggered by solid particles alone similar in size to macroparasites, independently of MYD88 signaling and at least partially dependent on inflammasome activation.