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Using a Bacterial Pathogen to Probe for Cellular and Organismic-level Host Responses
Published on: February 22, 2019
Detecting specific infections in children through host responses: a paradigm shift
Asuncion Mejias1, Nicolas M Suarez, Octavio Ramilo
1Division of Pediatric Infectious Diseases, Center for Vaccines and Immunity, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USA.
Insights
Analyzing blood cell gene expression (transcriptome) offers a powerful new way to diagnose infectious diseases and understand how the body fights them. This approach helps classify patients by disease severity, improving patient management.
Area of Science:
- Immunology
- Infectious Diseases
- Genomics
Background:
- Current infectious disease diagnosis relies heavily on pathogen detection.
- A comprehensive analysis of the host's immune response offers an alternative diagnostic strategy.
- Understanding host response is crucial for optimal patient classification and management.
Purpose of the Study:
- To review the diagnostic and management value of transcriptome analyses of blood leukocytes in infectious diseases.
- To highlight the potential of host response profiling as a complementary diagnostic tool.
- To explore the utility of transcriptomics in classifying disease severity.
Main Methods:
- Review of existing studies utilizing transcriptome analysis of blood leukocytes.
- Focus on microarray-based gene expression profiling.
- Validation of transcriptional signatures across diverse infectious agents and patient cohorts.
Main Results:
- Pathogen-specific transcriptional signatures identified in blood leukocytes for various viral and bacterial infections.
- Validated signatures for numerous diseases including malaria, dengue, tuberculosis, and HIV.
- Transcriptome analysis aids in understanding disease pathogenesis and objective patient classification by severity.
Conclusions:
- Blood transcriptome analyses are reproducible and valuable for studying host immune responses in clinical settings.
- Combining pathogen detection with host response assessment offers novel insights into disease dynamics.
- This integrated approach enhances understanding of host-pathogen interactions and clinical manifestations.
Purpose Of Review:
There is a need for improved diagnosis and for optimal classification of patients with infectious diseases. An alternative approach to the pathogen-detection strategy is based on a comprehensive analysis of the host response to the infection. This review focuses on the value of transcriptome analyses of blood leukocytes for the diagnosis and management of patients with infectious diseases.
Recent Findings:
Initial studies showed that RNA from blood leukocytes of children with acute viral and bacterial infections carried pathogen-specific transcriptional signatures. Subsequently, transcriptional signatures for several other infections have been described and validated in humans with malaria, dengue, salmonella, melioidosis, respiratory syncytial virus, influenza, tuberculosis, and HIV. In addition, transcriptome analyses represent an invaluable tool to understand disease pathogenesis and to objectively classify patients according to the clinical severity.
Summary:
Microarray studies have been shown to be highly reproducible using different platforms, and in different patient populations, confirming the value of blood transcriptome analyses to study pathogen-specific host immune responses in the clinical setting. Combining the detection of the pathogen with a comprehensive assessment of the host immune response will provide a new understanding of the correlations between specific causative agents, the host response, and the clinical manifestations of the disease.
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