Several bacterial pathogens of medical importance are able to persist and replicate inside host mononuclear phagocytes. Protective immunity depends on specific T lymphocytes that induce granulomatous lesions at the sites of bacterial multiplication. Listeria monocytogenes is an intracellular pathogen that replicates inside mononuclear phagocytes and hepatocytes of mice. Invasion from the phagosomal compartment into the cytoplasmic compartment is the principal mechanism of intracellular survival. Early in infection, resistance against L. monocytogenes is mediated by polymorphonuclear phagocytes which destroy infected liver cells, followed by natural killer cells which activate macrophages by means of interferon-gamma (refs 6, 7). A specific immune response by T cells then develops which leads to sterile eradication of the microbes. T cells are also responsible for the highly effective protection in vaccinated mice against secondary infections. Although the role of alpha beta T cells has been demonstrated in these immune responses, that of gamma delta T cells is unclear. Here we use mice that selectively lack either alpha beta or gamma delta T cells as a result of targeted germ-line mutations in their T-cell receptor genes to investigate the relative roles of these T-cell populations during experimental infection with L. monocytogenes. We find that in primary listeriosis, either alpha beta or gamma delta T cells are sufficient for early protection. Resistance to secondary infection is mediated mainly by alpha beta T cells but also involves gamma delta T cells. Thus alpha beta T-cell-deficient mice can be rendered partially resistant by vaccination, and gamma delta T cells are shown to be responsible for this protective effect. In infected gamma delta T-cell-deficient mice we noticed the appearance of unusual liver lesions, indicating that gamma delta T cells have a unique regulatory role in this bacterial infection.

This paper evaluates the loading and release properties of Tobramycin incorporated by adsorptive loading from a solution into plasma sprayed and biomimetically coated Hydroxyapatite (HA) fixation pins. The aim of this study is to contribute towards designing a functional implant surface offering local release of the antibiotic agent to prevent post-surgical infections. Cathodic arc deposition is used to coat stainless steel fixation pins with a bioactive, anatase phase dominated, TiO₂ coating onto which a HA layer is grown biomimetically. The loading and release properties are evaluated by studying the subsequent release of Tobramycin using high performance liquid chromatography and correlated to the differences in HA coating microstructure and the physical conditions under loading. The results from these studies show that a dual loading strategy consisting of a solution temperature of 90 °C and a pressure of 6 bar during a loading time of 5 min release a sufficient amount of Tobramycin to guarantee the inhibition of Staphylococcus aureus up to 2 days for plasma sprayed HA coatings and for 8 days for biomimetic coatings. The present study emphasizes the advantages of the nanoporous structure of biomimetically deposited HA over the more dense structure of plasma sprayed HA coatings in terms of antibiotic incorporation and subsequent sustained release and provides a valuable outline for the design of implant surfaces aiming for a fast-loading and controlled, local drug administration.

a b s t r a c tIn lower cancellous apparent bone density, it can be difficult to achieve adequate screw fixation and hence stable fracture fixation. Different strategies have been proposed, one of them is through augmentation using calcium phosphate cement in the region at or close to the screw thread itself. To support the hypothesis of an improved screw fixation technique by augmentation of the bone surrounding the implanted screw, in vivo biomechanical and densitometric studies are performed on rabbit specimen where normal and simulated weak bone quality are considered. In particular, the evolution of screw stability till 12 weeks following the implantation is quantified. A statistical significance in the pull out force for augmented versus non-augmented screws was found for the shorter time periods tested of r 5 days whilst the pull out force was found to increase with time for both augmented and non-augmented screws during the 12 week course of the study. The results of the study demonstrate that the use of an injectable calcium phosphate cement which sets in vivo can significantly improve screw pull out strength at and after implantation for normal and simulated weak bone quality.

After intradermal infection of mice with the obligatory intracellular parasite Leishmania major, Langerhans cells (LC) are intimately involved in the induction of the primary T-cell immune response. LC can phagocytose Leishmania and transport ingested parasites from the infected skin to the regional lymph nodes. Since TNFα and IL-1β have been shown to induce LC migration after epicutaneous exposure to skin-sensitizing chemicals, we investigated the involvement of both cytokines in the migration of Leishmania-infected LC. In addition, the relevance of two chemokines of the β subfamily, macrophage inflammatory protein 1α(MIP-1α) and macrophage chemoattractant protein 1 (MCP-1), was analyzed.In vivo depletion of TNFα significantly reduced the amount of infected LC and the parasite load in the draining lymph nodes. Administration of recombinant TNFα caused the reverse effect. In contrast, the depletion of IL1β enhanced the parasite-induced LC migration, whereas treatment with recombinant IL-1β, as well as recombinant MIP- c, reduced the rate of infected LC in the lymph nodes. MCP- did not influence LC migration. Our data demonstrate that TNFα and IL-1β are regulating the LCmediated transport of Leishmania and also provide evidence for the involvement of macrophage attractant chemokines in this process.