The research presented here aimed at using a Systems Biology approach to understand the mechanism governing a fruitful interaction between microbes and the human system. Systems Biology requires the acquisition of information on the different levels of regulation of a biological system and its integration in the development of models, that could predict the outcome of stimuli and changes in variables controlling the dynamic nature of the system. This work combined traditional wet-lab work and genome wide analyses of transcription and gene regulation, with computational and bioinformatic methods to dissect the response of dendritic cells to fungi, in particular to the harmless Saccharomyces cerevisiae. This work had two main goals: first, the implementation of an analytical approach that would facilitate the interpretation of the ‘-omics’ results and increase the comparability between different data sets, lessening the problems associated with the use of different types of data and array platforms; and the development of new pathway structure to allow temporal dissection of the immune response associated to the pattern recognition receptor sensing; secondly, by integration of different results, to investigate the immune response that discriminates between friends or foes. Combining transcriptional analysis with receptor-specific blocking and cytokine production assays, we determined that DCs respond differently to C. albicans and S. cerevisiae and in the latter case, the interplay between spores and yeasts is crucial for the commensalism of S. cerevisiae. The integration of a System Biology approach to functional data offers new interpretive clues to the mechanisms of fungal virulence: rather than dimorphism per se, the engagement of different recognition receptors on DCs might select the mode of fungal internalization and antigen presentation, condition the nature of the T-helper response and, ultimately, favor saprophytism or infection.
Of yeast and men: Dissecting the interaction between fungi and immune response / Rizzetto, L.. - (2010).
Of yeast and men: Dissecting the interaction between fungi and immune response
RIZZETTO, LISA
2010-01-01
Abstract
The research presented here aimed at using a Systems Biology approach to understand the mechanism governing a fruitful interaction between microbes and the human system. Systems Biology requires the acquisition of information on the different levels of regulation of a biological system and its integration in the development of models, that could predict the outcome of stimuli and changes in variables controlling the dynamic nature of the system. This work combined traditional wet-lab work and genome wide analyses of transcription and gene regulation, with computational and bioinformatic methods to dissect the response of dendritic cells to fungi, in particular to the harmless Saccharomyces cerevisiae. This work had two main goals: first, the implementation of an analytical approach that would facilitate the interpretation of the ‘-omics’ results and increase the comparability between different data sets, lessening the problems associated with the use of different types of data and array platforms; and the development of new pathway structure to allow temporal dissection of the immune response associated to the pattern recognition receptor sensing; secondly, by integration of different results, to investigate the immune response that discriminates between friends or foes. Combining transcriptional analysis with receptor-specific blocking and cytokine production assays, we determined that DCs respond differently to C. albicans and S. cerevisiae and in the latter case, the interplay between spores and yeasts is crucial for the commensalism of S. cerevisiae. The integration of a System Biology approach to functional data offers new interpretive clues to the mechanisms of fungal virulence: rather than dimorphism per se, the engagement of different recognition receptors on DCs might select the mode of fungal internalization and antigen presentation, condition the nature of the T-helper response and, ultimately, favor saprophytism or infection.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
