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Published on: August 11, 2018
T-Cell Responses Are Associated with Survival in Acute Melioidosis Patients
Kemajittra Jenjaroen1, Suchintana Chumseng1, Manutsanun Sumonwiriya1
1Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
Background:
Melioidosis is an increasingly recognised cause of sepsis and death across South East Asia and Northern Australia, caused by the bacterium Burkholderia pseudomallei. Risk factors include diabetes, alcoholism and renal disease, and a vaccine targeting at-risk populations is urgently required. A better understanding of the protective immune response in naturally infected patients is essential for vaccine design.
Methods:
We conducted a longitudinal clinical and immunological study of 200 patients with melioidosis on admission, 12 weeks (n = 113) and 52 weeks (n = 65) later. Responses to whole killed B. pseudomallei were measured in peripheral blood mononuclear cells (PBMC) by interferon-gamma (IFN-γ) ELIspot assay and flow cytometry and compared to those of control subjects in the region with diabetes (n = 45) and without diabetes (n = 43).
Results:
We demonstrated strong CD4+ and CD8+ responses to B. pseudomallei during acute disease, 12 weeks and 52 weeks later. 28-day mortality was 26% for melioidosis patients, and B. pseudomallei-specific cellular responses in fatal cases (mean 98 IFN-γ cells per million PBMC) were significantly lower than those in the survivors (mean 142 IFN-γ cells per million PBMC) in a multivariable logistic regression model (P = 0.01). A J-shaped curve association between circulating neutrophil count and mortality was seen with an optimal count of 4000 to 8000 neutrophils/μl. Melioidosis patients with known diabetes had poor diabetic control (median glycated haemoglobin HbA1c 10.2%, interquartile range 9.2-13.1) and showed a stunted B. pseudomallei-specific cellular response during acute illness compared to those without diabetes.
Conclusions:
The results demonstrate the role of both CD4+ and CD8+ T-cells in protection against melioidosis, and an interaction between diabetes and cellular responses. This supports development of vaccine strategies that induce strong T-cell responses for the control of intracellular pathogens such as B. pseudomallei.
Insights
Understanding the immune response to melioidosis is key for vaccine development. This study shows CD4+ and CD8+ T-cells are crucial for protection, with impaired responses in diabetic patients.
Area of Science:
- Immunology
- Infectious Diseases
- Vaccinology
Background:
- Melioidosis, caused by Burkholderia pseudomallei, is a significant cause of sepsis in Southeast Asia and Northern Australia.
- Risk factors include diabetes, alcoholism, and renal disease, highlighting the need for a targeted vaccine.
- Understanding the immune response in naturally infected individuals is vital for effective vaccine design.
Purpose of the Study:
- To investigate the longitudinal clinical and immunological responses in melioidosis patients.
- To identify key immune mechanisms involved in protection against B. pseudomallei infection.
- To assess the impact of diabetes on immune responses and disease outcomes.
Main Methods:
- A longitudinal study of 200 melioidosis patients was conducted, with immunological assessments at baseline, 12 weeks, and 52 weeks.
- Peripheral blood mononuclear cells (PBMC) were analyzed for interferon-gamma (IFN-γ) production using ELIspot and flow cytometry.
- Immune responses were compared between survivors and non-survivors, and between diabetic and non-diabetic patients.
Main Results:
- Strong CD4+ and CD8+ T-cell responses to B. pseudomallei were observed throughout the study period.
- Lower B. pseudomallei-specific cellular responses were associated with significantly higher 28-day mortality.
- Diabetic melioidosis patients exhibited poorer glycemic control and diminished cellular responses compared to non-diabetic individuals.
Conclusions:
- Both CD4+ and CD8+ T-cells play a critical role in protection against melioidosis.
- Diabetes significantly impacts cellular immune responses to B. pseudomallei infection.
- Vaccine strategies should aim to elicit robust T-cell responses for controlling intracellular pathogens like B. pseudomallei.
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