IL-17A and Streptococcus pneumoniae respiratory infection: Prospects for the development of new immunotherapies

Nasopharyngeal colonization by Streptococcus pneumoniae constitutes a pre-requisite for development of pneumonia and invasive pneumococcal diseases. Colonization is typically asymptomatic and is resolved due to a dynamic and complex interplay between microbiota, host immune system and environmental factors. Working with a murine model of pneumococcal nasopharyngeal colonization, we have shown that IL-17A is a key cytokine in this process, since Il17a-/- mice were persistently colonized for up to 6 months whereas wild type mice cleared colonization in 10 days. We are currently trying to elucidate the downstream mechanisms that may account for the phenotype showed in Il17a-/- mice, including the production of specific antibodies, as well as the recruitment of innate cells and the expression of immune mediators in WT and Il17a-/- mice. On the other hand, we have studied the role of IL-17A in the development of protective immunity against acute pneumococcal pneumonia. Previously, we showed that prior sublethal infection resulted in solid protection against invasive pneumonia which is associated with over expression of IL-17A together with the presence of Th17 cells in the lungs. However, Il17a-/- mice showed same level of protection than WT, demonstrating that IL-17A by itself is not essential for protective immunity. Interestingly Il17a-/- mice showed overexpression of other IL-17 related genes suggesting a complex network where compensatory effects may be occurring. Finally, we have developed and tested alternative immunotherapies against pneumococcal pneumonia, and have evaluated the role of IL17A in the protection afforded. Overall, we believe that deciphering the molecular basis of protective immunity will result in the development of new cost-effective immunotherapies against pneumococcal pneumonia

The use of salmonella vaccines as carriers for heterologous antigens

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Comparative genome analysis of Salmonella Enteritidis PT4 and Salmonella Gallinarum 287/91 provides insights into evolutionary and host adaptation pathways

We have determined the complete genome sequences of a host-promiscuous Salmonella enterica serovar Enteritidis PT4 isolate P125109 and a chicken-restricted Salmonella enterica serovar Gallinarum isolate 287/91. Genome comparisons between these and other Salmonella isolates indicate that S. Gallinarum 287/91 is a recently evolved descendent of S. Enteritidis. Significantly, the genome of S. Gallinarum has undergone extensive degradation through deletion and pseudogene formation. Comparison of the pseudogenes in S. Gallinarum with those identified previously in other host-adapted bacteria reveals the loss of many common functional traits and provides insights into possible mechanisms of host and tissue adaptation. We propose that experimental analysis in chickens and mice of S. Enteritidis-harboring mutations in functional homologs of the pseudogenes present in S. Gallinarum could provide an experimentally tractable route toward unraveling the genetic basis of host adaptation in S. enterica