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Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. Its polysaccharide capsule causes resistance to phagocytosis and interferes with the innate immune system's ability to clear infections at an early stage. Nevertheless, we found that encapsulated pneumococci are sensitive to killing by a human neutrophil granule extract. We fractionated the extract by high-performance liquid chromatography and identified α-defensins by mass spectrometry as the proteins responsible for killing pneumococci. Analysis of sensitivity to the commercial α-defensins human neutrophil proteins 1 to 3 (HNP1-3) confirmed these findings. We analyzed the sensitivities of different pneumococcal strains to HNP1-3 and found that encapsulated strains are efficiently killed at physiological concentrations (7.5 μg/ml). Surprisingly, nonencapsulated, nonvirulent pneumococci were significantly less sensitive to α-defensins. The proposed mechanisms of α-defensin resistance in nonencapsulated pneumococci is surface charge modification, e.g., by introduction of positive charge by d -alanylation of surface-exposed lipoteichoic acids. These mechanisms are surmounted by the presence of the capsule, which we hypothesize is masking these charge modifications. Hence, α-defensins in the phagolysosome of neutrophils possibly contribute to intracellular killing after antibody-mediated opsonophagocytosis of encapsulated pneumococci.

The phenotypic and functional changes of glycolipid presented by CD1d(glycolipid/CD1d) specific Vα14+T cells in the liver of mice at early stages of bacterial infection were investigated. AfterListeria monocytogenesinfection or interleukin-12 (IL-12) treatment, α-galactosylceramide/CD1d tetramer-reactive (α-GalCer/CD1d+) T cells coexpressing natural killer (NK) 1.1 marker became undetectable and, concomitantly, cells lacking NK1.1 emerged in both euthymic and thymectomized animals. Depletion of the NK1.1+subpopulation prevented the emergence of α-GalCer/CD1d+NK1.1−T cells. Before infection, NK1.1+, rather than NK1.1−, α-GalCer/CD1d+T cells coexpressing CD4 were responsible for IL-4 production, whereas gamma interferon (IFN-γ) was produced by cells regardless of NK1.1 or CD4 expression. After infection, IL-4-secreting cells became undetectable among α-GalCer/CD1d+T cells, but considerable numbers of IFN-γ-secreting cells were found among NK1.1−, but not NK1.1+, cells lacking CD4. Thus, NK1.1 surface expression and functional activities of Vα14+T cells underwent dramatic changes at early stages of listeriosis, and these alterations progressed in a thymus-independent manner. In mutant mice lacking all α-GalCer/CD1d+T cells listeriosis was ameliorated, suggesting that the subtle contribution of the NK1.1−T-cell subset to antibacterial protection is covered by more profound detrimental effects of the NK1.1+T-cell subset.

A multiparameter selection of Helicobacter pylori antigens for vaccine development identified 15 candidates, 6 of which are known protective antigens. Two novel antigens with low homology to other organisms (HP0231 and HP0410) were overexpressed and purified with high yields. Both confer protective immunity in the mouse Helicobacter infection model.

Vaccination of interleukin-4 (IL-4) receptor α (IL-4Rα) chain-deficient BALB/c mice withHelicobacter pyloriurease and cholera toxin or with urease-expressing, live attenuatedSalmonella entericaserovar Typhimurium cells revealed that protection againstH. pyloriinfection is independent of IL-4- or IL-13-mediated signals. A comparison of male and female mice suggests a sexual dimorphism in the extent of bacterial colonization that is particularly evident in the absence of the IL-4Rα chain.