Transcriptional response in the peripheral blood of patients infected with Salmonella enterica serovar Typhi

Abstract

We used microarrays and transcriptional profiling of peripheral blood to investigate the host response of 29 individuals who contracted typhoid fever in the Mekong Delta region of Vietnam. Samples were taken over a nine month period encompassing acute disease, convalescence, and recovery. We found that typhoid fever induced a distinct and highly reproducible signature in the peripheral blood that changed during treatment and convalescence, returning in the majority of cases to the ''normal'' profile as measured in healthy uninfected controls. Unexpectedly, there was a strong, distinct signature of convalescence present at day 9 after infection that remained virtually unchanged one month after acute infection and in some cases persisted as long as nine months despite a complete clinical recovery in all patients. Patients who retain the convalescent signature may be genetically or temporarily incapable of developing an effective immune response and may be more susceptible to reinfection, relapse, or the establishment of a carrier state.immune response ͉ microbe-host interaction ͉ transcriptional profiling ͉ typhoid fever

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

“…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. 28 In the most susceptible B6.MOLF-Ity/Ity2.RecD congenic strain, three clusters of genes showed significant specific profiles. They include genes involved in erythropoiesis and iron metabolism, type 1 IFN-inducible genes and genes regulated by TRP53.…”

“…6,29 In humans, the presence of anemia during Salmonella typhi infection is well documented and correlates with reduced abundance of genes associated with erythroid differentiation in the peripheral blood. 28 The second specific signature observed in B6.MOLF-Ity/Ity2.RecD involved upregulation of type 1 IFN signaling. We have shown recently that increased type 1 IFN signaling is detrimental during Salmonella infection in the mouse.…”

Epidemiology, Clinical Presentation, Laboratory Diagnosis, Antimicrobial Resistance, and Antimicrobial Management of Invasive Salmonella Infections

“…Proteomic and immunoscreening approaches are being used to seek antibodies and antigens that have a higher level of specificity than those used currently used (306)(307)(308)(309)(310)(311). Analysis of bacterial gene expression in typhoid and paratyphoid may also lead to new diagnostic tests (312)(313)(314). …”

Interactome analysis of longitudinal pharyngeal infection of cynomolgus macaques by group A Streptococcus

“…Advances in genome-wide analyses occurring in the last decade have facilitated the study of global transcriptome changes that occur during microbial infection. The vast majority of these studies, such as the recent investigation of typhoid fever (1), have addressed the pathogen or host transcriptome at a single or relatively few points in the infection cycle. Although much has been learned, a poorly understood area of infectious disease research revolves around the simultaneous changes in the host and pathogen transcriptomes occurring throughout the entire course of infection.…”