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Diabetes alters immune response patterns to acute melioidosis in humans
Barbara Kronsteiner1,2, Panjaporn Chaichana3, Manutsanun Sumonwiriya3
1Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
Abstract:
Diabetes mellitus (DM) is a serious global health problem currently affecting over 450 million people worldwide. Defining its interaction with major global infections is an international public health priority. Melioidosis is caused by Burkholderia pseudomallei, an exemplar pathogen for studying intracellular bacterial infection in the context of DM due to the 12-fold increased risk in this group. We characterized immune correlates of survival in peripheral blood of acute melioidosis patients with and without DM and highlight different immune response patterns. We demonstrate the importance of circulating NK cells and show that CX3CR1 expression on lymphocytes is a novel correlate of survival from acute melioidosis. Furthermore, excessive serum levels of IL-15 and IL-18BP contribute to poor outcome independent of DM comorbidity. CD8+ T cells and granzyme B expression in NK cells are important for survival of non-DM patients, whereas high antibody titers against B. pseudomallei and double-negative T cells are linked to survival of DM patients. Recall responses support a role of γδ T-cell-derived IFN-γ in the establishment of protective immunity in the DM group. Defining the hallmarks of protection in people with DM is crucial for the design of new therapies and vaccines targeting this rapidly expanding risk group.
Insights
Diabetes mellitus (DM) patients exhibit distinct immune responses to melioidosis. Understanding these differences, particularly involving NK cells and T cells, is vital for developing targeted therapies and vaccines for this high-risk group.
Area of Science:
- Immunology
- Infectious Diseases
- Global Health
Background:
- Diabetes mellitus (DM) affects over 450 million globally, increasing susceptibility to infections.
- Melioidosis, caused by Burkholderia pseudomallei, poses a 12-fold higher risk for individuals with DM.
- Understanding immune responses in DM patients with melioidosis is critical for public health.
Purpose of the Study:
- To characterize immune correlates of survival in acute melioidosis patients with and without DM.
- To identify distinct immune response patterns associated with outcomes in these patient groups.
- To explore novel immune markers for predicting survival in DM patients with melioidosis.
Main Methods:
- Analysis of peripheral blood immune cells and serum cytokines in acute melioidosis patients.
- Comparison of immune profiles between patients with and without DM.
- Assessment of NK cell activity, T cell subsets, and antibody titers against B. pseudomallei.
Main Results:
- CX3CR1 expression on lymphocytes is a novel correlate of survival.
- Elevated IL-15 and IL-18BP levels correlate with poor outcomes, independent of DM.
- Specific immune responses differ: CD8+ T cells and NK granzyme B for non-DM, antibody titers and double-negative T cells for DM patients.
Conclusions:
- Immune responses to melioidosis vary significantly between individuals with and without DM.
- Identifying DM-specific protective immunity, including γδ T-cell IFN-γ, is crucial for vaccine and therapy development.
- Targeting these immune hallmarks can improve outcomes for the expanding population of DM patients at risk for severe infections.
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