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PLoS One. 2018 Jan 29;13(1):e0192082. doi: 10.1371/journal.pone.0192082. eCollection 2018.

Shared and organism-specific host responses to childhood diarrheal diseases revealed by whole blood transcript profiling.

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Benaroya Research Institute at Virginia Mason, Seattle, Washington, United States of America.
Infectious Diseases Research Unit, and Pediatric Emergency Department, Hospital General O'Horan, Mérida, Yucatán, Mexico.
Department of Epidemiology and Biostatistics, Michigan State University, Lansing, Michigan, United States of America.
Department of Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.
Department of Molecular Biomedicine, CINVESTAV-IPN, México DF, México.
The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, United States of America.


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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