Micrometer-Sized Titanium Particles Can Induce Potent Th2-Type Responses through TLR4-Independent Pathways

Wear debris in joint replacements has been suggested as a cause of associated tissue-damaging inflammation. In this study, we examined whether solid titanium microparticles (mTi) of sufficient size to accumulate as wear debris could stimulate innate or adaptive immunity in vivo. mTi, administered in conjunction with OVA, promoted total and Ag-specific elevations in serum IgE and IgG1. Analysis of transferred transgenic OVA-specific naive T cells further showed that mTi acted as an adjuvant to drive Ag-specific Th2 cell differentiation in vivo. Assessment of the innate response indicated that mTi induced rapid recruitment and differentiation of alternatively activated macrophages in vivo, through IL-4- and TLR4-independent pathways. These studies suggest that solid microparticles alone can act as adjuvants to induce potent innate and adaptive Th2-type immune responses and further suggest that wear debris in joint replacements may have Th2-type inflammatory properties.