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Rotavirus infection alters peripheral T-cell homeostasis in children with acute diarrhea
Yuhuan Wang1, Penelope H Dennehy, Harry L Keyserling
1Division of Viral Diseases, Scientific Resources Program, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Insights
Rotavirus infection in children triggers strong antiviral and B-cell responses but temporarily disrupts T-cell balance. Immune cells in peripheral blood mononuclear cells (PBMC) show altered gene expression and T-cell populations.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Rotavirus is a common cause of severe diarrhea in children worldwide.
- Understanding the immune response to rotavirus is crucial for developing effective treatments and prevention strategies.
- Previous studies have indicated immune system alterations during rotavirus infection, but detailed molecular and cellular changes remain to be fully elucidated.
Purpose of the Study:
- To compare gene expression patterns and lymphocyte phenotypes in children with rotavirus diarrhea versus healthy children.
- To investigate the molecular and cellular immune responses, including cytokine production and T-cell/B-cell dynamics, during acute and convalescent phases of rotavirus infection.
Main Methods:
- Peripheral blood mononuclear cells (PBMC) were analyzed from children with rotavirus diarrhea and healthy controls.
- Techniques included DNA microarray for gene expression profiling, quantitative PCR for specific gene analysis, and flow cytometry for cell surface marker detection.
- Analysis focused on gene expression related to inflammation, antiviral responses, and lymphocyte differentiation, activation, and survival.
Main Results:
- Rotavirus infection significantly increased the expression of genes encoding proinflammatory cytokines and interferon-stimulated proteins.
- Activation of B-lymphocyte differentiation, maturation, activation, and survival genes was observed, alongside increased CD83 and CD69 expression on B cells.
- A transient decrease in total T lymphocytes, including CD4 and CD8 subsets, was noted, with altered gene expression related to T-cell development; T-cell proportions normalized during convalescence.
Conclusions:
- Rotavirus infection in children induces potent proinflammatory and antiviral immune responses and robust B-cell activation.
- The infection temporarily disrupts peripheral T-cell homeostasis, characterized by reduced T-cell populations and altered gene expression.
- Immune cell activation markers, such as CD83, remain elevated on T lymphocytes even after the acute phase, suggesting lasting immune modulation.
Abstract:
The patterns of gene expression and the phenotypes of lymphocytes in peripheral blood mononuclear cells (PBMC) from children with diarrhea caused by rotavirus and healthy children were compared by using DNA microarray, quantitative PCR, and flow cytometry. We observed increased expression of a number of genes encoding proinflammatory cytokines and interferon or interferon-stimulated proteins and demonstrated activation of some genes involved in the differentiation, maturation, activation, and survival of B lymphocytes in PBMC of patients with rotavirus infection. In contrast, we observed a consistent pattern of lower mRNA levels for an array of genes involved in the various stages of T-cell development and demonstrated a reduction in total lymphocyte populations and in the proportions of CD4 and CD8 T lymphocytes from PBMC of patients. This decreased frequency of T lymphocytes was transient, since the proportions of T lymphocytes recovered to almost normal levels in convalescent-phase PBMC from most patients. Finally, rotavirus infection induced the activation and expression of the early activation markers CD83 and CD69 on a fraction of CD19 B cells and the remaining CD4 and CD8 T lymphocytes in acute-phase PBMC of patients; the expression of CD83 continued to be elevated and was predominantly exhibited on CD4 T lymphocytes in convalescent-phase PBMC. On the basis of these findings at the molecular, phenotypic, and physiologic levels in acute-phase PBMC, we conclude that rotavirus infection induces robust proinflammatory and antiviral responses and B-cell activation but alters peripheral T-cell homeostasis in children.
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