Priming by Streptococcus pneumoniae causes changes in gene expression in Drosophila melanogaster
- Junaid Ziauddin.
- Aug. 2013.
- Physical description
- online resource (xii, 140 pages) : illustrations (some color)
- Includes bibliographical references (p. 128-140). 205 refs.
- Insects are typically described as having no memory yet they can be primed by past exposure to survive a specific pathogenic challenge. To determine how a primed immune response might work in the context of a transcriptional response to a pathogen, we performed a microarray analysis that identified genes modulated by priming during a S. pneumoniae infection in Drosophila melanogaster. We followed 22 transcripts at a high level of resolution using qRT-PCR of tight timelines of infected primed and naïve flies. We knocked down expression of 17 of these transcripts/genes and observed changes in survival and bacterial growth dynamics. We found that priming affected the transcriptional response in three ways. First, the basal levels of some transcripts changed permanently upon priming. Second, the induced maximal expression level of genes was altered between the first and second infection. Third, there were changes in sensitivity where genes were induced at earlier times in the infection in the primed flies. We hypothesized that these changes are evolved to adapt, where the fly's immunity changes in a fashion that allows it to respond more effectively to that infection in subsequent exposures. We highlight 5 genes that follow our gene induction model and show that when knocked down, primed flies exhibit survival and bacterial growth phenotypes that demonstrate their important role in the primed response. These data show how a simple signaling network can possess memory which allows it to respond more effectively to threats based upon past experiences. We also added Serratia marcescens to the repertoire of pathogens that induce the primed immune response. We showed that this memory lasts for the life of the fly and the Toll pathway is necessary for the response. We demonstrated that Serratia is not cleared in primed flies despite longer survival times, indicating a tolerance effect. We found the highest protection to be species specific and nutrient deprivation to negatively impact priming. It is the first time gram-negative bacteria have been characterized in the primed response and the first time tolerance-based priming against any pathogen has been demonstrated in Drosophila.
- Drosophila > immunology
- Host-Pathogen Interactions
- Streptococcus pneumoniae > immunology
- Drosophila > genetics
- Serratia marcescens > immunology
- Transcription Factors
- Publication date
- Submitted to the Department of Microbiology and Immunology and the Committee on Graduate Studies of Stanford University.
- Thesis (Ph.D.)--Stanford University, 2013.