Absence of Both IL-7 and IL-15 Severely Impairs the Development of CD8+ T Cell Response against Toxoplasma gondii

CD8+ T cells play an essential role in the protection against both acute as well as chronic Toxoplasma gondii infection. Although the role of IL-15 has been reported to be important for the development of long-term CD8+ T cell immunity against the pathogen, the simultaneous roles played by both IL-15 and related γ-chain family cytokine IL-7 in the generation of this response during acute phase of infection has not been described. We demonstrate that while lack of IL-7 or IL-15 alone has minimal impact on splenic CD8+ T cell maturation or effector function development during acute Toxoplasmosis, absence of both IL-7 and IL-15 only in the context of infection severely down-regulates the development of a potent CD8+ T cell response. This impairment is characterized by reduction in CD44 expression, IFN-γ production, proliferation and cytotoxicity. However, attenuated maturation and decreased effector functions in these mice are essentially downstream consequences of reduced number of antigen-specific CD8+ T cells. Interestingly, the absence of both cytokines did not impair initial CD8+ T cell generation but affected their survival and differentiation into memory phenotype IL-7Rαhi cells. Significantly lack of both cytokines severely affected expression of Bcl-2, an anti-apoptotic protein, but minimally affected proliferation. The overarching role played by these cytokines in eliciting a potent CD8+ T cell immunity against T. gondii infection is further evidenced by poor survival and high parasite burden in anti IL-7 treated IL-15−/− mice. These studies demonstrate that the two cytokines, IL-7 and IL-15, are exclusively important for the development of protective CD8+ T cell immune response against T. gondii. To the best of our knowledge this synergism between IL-7 and IL-15 in generating an optimal CD8+ T cell immunity against intracellular parasite or any other infectious disease model has not been previously reported

The survival of resin modified glass ionomer and stainless steel crown restorations in primary molars, placed in a specialist paediatric dental practice.

Aims To prospectively report on the survival of resin-modified glass ionomer cement (RMGIC), photac-fil and pre-formed stainless steel crown (SSC) restorations in primary molar teeth placed over a seven-year period in a specialist paediatric dental practice under private contract of remuneration.Method All primary molar restorations placed by a specialist paediatric dentist over a seven-year period were reviewed and the outcome results recorded. Data were recorded at review visits until June 30, 2003. Data recorded included Class I restorations, Class II restorations and SSC. The Class II cavities were either mesial or distal, with or without buccal/palatal extensions. If both proximal surfaces were decayed or if after cavity preparation the resultant outline form was significantly larger than the minimal classical form, RMGIC was not used; an SSC was placed instead. Stainless steel crown preparation followed conventional guidelines. The crowns were cemented with reinforced zinc oxide and eugenol ( Kalzinol). The status was recorded as satisfactory restoration, tooth exfoliated, tooth extracted for orthodontic reasons with the date of extraction, or needing replacement. If replaced then the reason for replacement was also recorded.Results A total of 544 Class I RMGICs, 962 Class II RMGICs, and 1,010 SSCs were placed. At the last review of each restoration, 98.3% of Class I, 97.3% of Class II RMGICs and 97.0% of SSCs were either satisfactory or withdrawn intact.Conclusion Under the conditions of private specialist practice-based study SSCs continued to prove very successful for the restoration of larger cavities and for pulp-treated primary molar teeth. For the smaller cavities RMGIC were also very successful

Transcriptomic insights into the early host-pathogen interaction of cat intestine with Toxoplasma gondii

Abstract Background Although sexual reproduction of the parasite Toxoplasma gondii exclusively occurs in the cat intestine, knowledge about the alteration of gene expression in the intestine of cats infected with T. gondii is still limited. Here, we investigated the temporal transcriptional changes that occur in the cat intestine during T. gondii infection. Methods Cats were infected with 100 T. gondii cysts and their intestines were collected at 6, 12, 18, 24, 72 and 96 hours post-infection (hpi). RNA sequencing (RNA-Seq) Illumina technology was used to gain insight into the spectrum of genes that are differentially expressed due to infection. Quantitative RT-PCR (qRT-PCR) was also used to validate the level of expression of a set of differentially expressed genes (DEGs) obtained by sequencing. Results Our transcriptome analysis revealed 2363 DEGs that were clustered into six unique patterns of gene expression across all the time points after infection. Our analysis revealed 56, 184, 404, 508, 400 and 811 DEGs in infected intestines compared to uninfected controls at 6, 12, 18, 24, 72 and 96 hpi, respectively. RNA-Seq results were confirmed by qRT-PCR. DEGs were mainly enriched in catalytic activity and metabolic process based on gene ontology enrichment analysis. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that transcriptional changes in the intestine of infected cats evolve over the course of infection, and the largest difference in the enriched pathways was observed at 96 hpi. The anti-T. gondii defense response of the feline host was mediated by Major Histocompatibility Complex class I, proteasomes, heat-shock proteins and fatty acid binding proteins. Conclusions This study revealed novel host factors, which may be critical for the successful establishment of an intracellular niche during T. gondii infection in the definitive feline host