Shared and organism-specific host responses to childhood diarrheal diseases revealed by whole blood transcript
Hannah A DeBerg1, Mussaret B Zaidi2,3, Matthew C Altman1,4
1Benaroya Research Institute at Virginia Mason, Seattle, Washington, United States of America.
Insights
Identifying the cause of childhood diarrhea is difficult. This study found unique host gene signatures in blood that can help distinguish between Salmonella, Shigella, and rotavirus infections, improving diagnosis and treatment.
Area of Science:
- Infectious Diseases
- Genomics
- Pediatrics
Background:
- Diarrheal diseases are a major cause of mortality in children under five, particularly in developing nations.
- Current pathogen identification methods are time-consuming and costly, limiting targeted therapy for childhood diarrhea.
- Rapid diagnostic biomarkers are needed to improve treatment and outcomes for pediatric diarrheal diseases.
Purpose of the Study:
- To identify host gene expression signatures associated with specific bacterial and viral pathogens causing diarrheal disease in children.
- To evaluate the potential of host response transcript signatures for differentiating between common etiologic agents of childhood diarrhea.
Main Methods:
- RNA sequencing was performed on blood samples from children presenting with diarrheal disease in an emergency room setting.
- Host gene expression profiles were analyzed to identify signatures specific to known pathogens (Salmonella, Shigella, rotavirus, E. coli).
- Differential gene expression analysis was used to compare host responses between different pathogen infections and healthy controls.
Main Results:
- Distinct host response gene signatures were identified for Salmonella, Shigella, and rotavirus infections, differentiating them from each other and from healthy controls.
- Shigella infections showed differential expression of genes involved in chemokine receptor and inflammasome signaling (e.g., CCR3, CXCR8, NLRC4).
- Rotavirus infections were associated with differential expression of interferon response genes (e.g., IFI44, OASL). E. coli did not yield a distinct signature.
Conclusions:
- Host peripheral immune responses vary significantly based on the specific pathogen causing diarrheal disease in children.
- Host response transcript signatures show promise for diagnosing the etiologic agent of childhood diarrheal diseases.
- Limitations exist for using transcript signatures, highlighting the need for further research and validation.
Abstract:
Globally, diarrheal diseases are a leading cause of death in children under five and disproportionately affect children in developing countries. Children who contract diarrheal diseases are rarely screened to identify the etiologic agent due to time and cost considerations associated with pathogen-specific screening and hence pathogen-directed therapy is uncommon. The development of biomarkers to rapidly identify underlying pathogens could improve treatment options and clinical outcomes in childhood diarrheal diseases. Here, we perform RNA sequencing on blood samples collected from children evaluated in an emergency room setting with diarrheal disease where the pathogen(s) present are known. We determine host response gene signatures specific to Salmonella, Shigella and rotavirus, but not E. coli, infections that distinguish them from each other and from healthy controls. Specifically, we observed differential expression of genes related to chemokine receptors or inflammasome signaling in Shigella cases, such as CCR3, CXCR8, and NLRC4, and interferon response genes, such as IFI44 and OASL, in rotavirus cases. Our findings add insight into the host peripheral immune response to these pathogens, and suggest strategies and limitations for the use host response transcript signatures for diagnosing the etiologic agent of childhood diarrheal diseases.
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