Insights into host responses against pathogens from transcriptional profiling

Abstract

DNA microarrays have allowed us to monitor the effects of pathogens on host-cell gene expression programmes in great depth and on a broad scale. The comparison of results that have been generated by these studies is complex, and such a comparison has not previously been attempted in a systematic manner. In this review, we have collated and compared published transcriptional-profiling data from 32 studies that involved 77 different host-pathogen interactions, and have defined a common host-transcriptional-response. We outline gene expression patterns in the context of Toll-like receptor and pathogen-mediated signalling pathways, and summarize the contributions that transcriptional-profiling studies have made to our understanding of the infectious disease process.

Incremental expression of Tlr4 correlates with mouse resistance to Salmonella infection and fine regulation of relevant immune genes

“…(Figure 7d-f) all belong to what has been described as the common host response to infection. 17 Il1b, encoding the pro-inflammatory cytokine IL-1b, was strongly and similarly upregulated in all three groups at days 4 and 8 post-infection. Il12a, Il12b (at day 4) and Ifng were all upregulated during Salmonella infection, indicating activation of the IL-12-IFNg axis shown to be important in immunity to Salmonella.…”

“…These results indicate a role for the level of Tlr4 expression in controlling the bacterial replication during the first 10 days of infection. However, in F1Tg388 mice, the spleen and liver bacterial load eventually increased during the late phase of infection to reach lethal numbers around days [15][16][17][18][19][20]. Therefore, the increased protection conferred by incremental Tlr4 expression appears to be limited to the early phase of infection suggesting that despite a robust innate immune response, the host is unable to mount protective adaptive immunity resulting in long-term control of the bacterial replication.…”

Refinement of the genetics of the host response to Salmonella infection in MOLF/Ei: regulation of type 1 IFN and TRP3 pathways by Ity2

“…4,6,9 The set of genes defined in our analysis was also shown to be induced in several human cell types in response to different pathogens in vitro, and were suggested to belong to a common host response signature. 23 In addition, the importance of the interleukin-12/IFN-g axis in the host response to Salmonella-induced systemic disease in mice [24][25][26] and salmonellosis in humans 27 is well known. Additional data to support these observations came from recent publications reporting the induction of large proportion of genes induced by IFN-g in the peripheral blood of patients during the acute phase of typhoid fever.…”

Transcriptome analysis of porcine PBMCs after in vitro stimulation by LPS or PMA/ionomycin using an expression array targeting the pig immune response

“…The development of DNA chips for genome-wide expression studies [2] and the next generation sequencing (NGS) technology for much deeper transcriptome analyses [3] are complementary approaches to conduct functional genomics research [4]. DNA chip-based transcriptome analyses are efficient to study host-pathogen interactions using either pathogen transcriptomes [5] or host transcriptomes [6-9] or both pathogen and host modifications of the transcriptome during infection [10]. Thus, DNA chips are still highly valuable to analyze large numbers of samples and in the case of domestic animals, it is essential to develop well-annotated DNA chips and sequence-based transcriptome using the NGS technology.…”