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Early Transcriptional Responses to Human Paratyphoid Challenge

ABSTRACT: Early Transcriptional Responses to Human Paratyphoid Challenge

PROVIDER: PRJNA929287 | ENA |

REPOSITORIES: ENA

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Early Transcriptional Responses to Human Paratyphoid Challenge

Project description:The whole blood transcriptome 12 hours after challenge with S. Paratyphi A. Samples were collected in a study aiming to find the challenge dose giving a 60-75% attack rate, published in Dobinson et al. PMID: 28158395. Participants were challenged with S. Paratyphi A NVGH308 strain suspended in sodium bicarbonate. Enteric fever was diagnosed based on oral temperature or positive blood culture. Participants were treated with antibiotics either following diagnosis or 14 days without diagnosis. Paired baseline samples are available under Series GSE114033.

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Early transcriptional responses to human enteric fever challenge.

Project description:Enteric fever, caused by oral infection with typhoidal Salmonella serovars, presents as a non-specific febrile illness preceded by an incubation period of 5 days or more. The enteric fever human challenge model provides a unique opportunity to investigate the innate immune response during this incubation period, and how this response is altered by vaccination with the Vi polysaccharide or conjugate vaccine. We find that on the same day as ingestion of typhoidal Salmonella, there is already evidence of an immune response, with 199 genes upregulated in the peripheral blood transcriptome 12 hours post-challenge (false discovery rate <0.05). Gene sets relating to neutrophils, monocytes, and innate immunity were over-represented (false discovery rate <0.05). Estimating cell proportions from gene expression data suggested a possible increase in activated monocytes 12 hours post-challenge (P = 0.036, paired Wilcoxon signed-rank test). Furthermore, plasma TNF-α rose following exposure (P = 0.011, paired Wilcoxon signed-rank test). There were no significant differences in gene expression (false discovery rate <0.05) in the 12 hours response between those who did and did not subsequently develop clinical or blood culture confirmed enteric fever or between vaccination groups. Together, these results demonstrate early perturbation of the peripheral blood transcriptome after enteric fever challenge and provide initial insight into early mechanisms of protection.

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