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γδ T Cells Mediate Protection against Neutrophil-associated Lung Inflammation in Pulmonary Melioidosis
Shelton W Wright1, Sineenart Sengyee2, Peeraya Ekchariyawat3
1Division of Pediatric Critical Care Medicine, Department of Pediatrics.
Abstract:
Pulmonary melioidosis is a severe tropical infection caused by Burkholderia pseudomallei and is associated with high mortality, despite early antibiotic treatment. γδ T cells have been increasingly implicated as drivers of the host neutrophil response during bacterial pneumonia, but their role in pulmonary melioidosis is unknown. Here, we report that in patients with melioidosis, a lower peripheral blood γδ T-cell concentration is associated with higher mortality, even when adjusting for severity of illness. γδ T cells were also enriched in the lung and protected against mortality in a mouse model of pulmonary melioidosis. γδ T-cell deficiency in infected mice induced an early recruitment of neutrophils to the lung, independent of bacterial burden. Subsequently, γδ T-cell deficiency resulted in increased neutrophil-associated inflammation in the lung as well as impaired bacterial clearance. In addition, γδ T cells influenced neutrophil function and subset diversity in the lung after infection. Our results indicate that γδ T cells serve a novel protective role in the lung during severe bacterial pneumonia by regulating excessive neutrophil-associated inflammation.
Insights
Lower levels of gamma delta T cells (γδ T cells) correlate with higher mortality in pulmonary melioidosis. These immune cells protect against severe lung inflammation and improve bacterial clearance in a mouse model.
Area of Science:
- Immunology
- Infectious Diseases
- Pulmonology
Background:
- Pulmonary melioidosis, caused by Burkholderia pseudomallei, is a severe tropical infection with high mortality.
- Gamma delta T cells (γδ T cells) are known to influence neutrophil responses in bacterial pneumonia, but their role in melioidosis is unclear.
Purpose of the Study:
- To investigate the role of γδ T cells in pulmonary melioidosis and their impact on host defense and mortality.
Main Methods:
- Analysis of peripheral blood γδ T-cell counts in melioidosis patients.
- Assessment of γδ T-cell presence and function in lung tissue.
- Evaluation of mortality and lung pathology in a mouse model of pulmonary melioidosis with and without γδ T cells.
Main Results:
- Lower peripheral blood γδ T-cell counts were associated with increased mortality in melioidosis patients, independent of illness severity.
- γδ T cells were found to be enriched in the lungs and conferred protection against mortality in mice.
- γδ T-cell deficiency led to increased neutrophil recruitment and inflammation in the lungs, alongside impaired bacterial clearance.
Conclusions:
- γδ T cells play a crucial protective role in pulmonary melioidosis by regulating excessive neutrophil-driven inflammation.
- Maintaining adequate γδ T-cell levels may be important for improving outcomes in severe bacterial pneumonia.
