Osteopontin supports neutrophil survival and function in polymicrobial infection. (P1281)

Abstract

Abstract Oral infections are among the most prevalent bacterial infections: they are polymicrobial and refractory to antibiotic treatment. Understanding the host response to these infections is critical for their ultimate control. Osteopontin (OPN), a secreted phosphorylated integrin binding protein, has been previously shown to protect against inflammation in a mouse model of endodontic infection. The objective of this work was to determine the mechanism by which OPN protects against polymicrobial infection. Here we have used a titanium chamber model to analyze the innate immune response to polymicrobial infection in mice in the presence or absence of OPN. Chambers were implanted subcutaneously in WT and OPN-deficient mice, and inoculated with a mixture of four endodontic pathogens. The fluid within the chamber was sampled at different times after infection. 80-90% of the cells appearing in the chamber fluid were Ly6G+ neutrophils. At early times, there were significantly lower numbers of cells in the absence of OPN and the viability of these cells was lower than in WT mice. In addition, there were significantly higher numbers of live bacteria in the absence of OPN. These results suggest that OPN functions to protect neutrophils from apoptosis and is required for maximal bacterial killing during bacterial infection. Our results are also consistent with a role for OPN in neutrophil function. Analysis of the integrins responsible for these effects is underway.