Association of Diabetes Mellitus With a Shared Hyperinflammatory Immune Response in Patients With Melioidosis and Patients With Tuberculosis: An Observational Case-Control Study
9
Issued Date
2026-06-01
Resource Type
eISSN
23288957
Scopus ID
2-s2.0-105042167172
Journal Title
Open Forum Infectious Diseases
Volume
13
Issue
6
Rights Holder(s)
SCOPUS
Bibliographic Citation
Open Forum Infectious Diseases Vol.13 No.6 (2026)
Suggested Citation
Rongkard P.G., Kronsteiner B.A., Eckold C., Chamnan P.A., Chumseng S.A., Ali M.D., Hill J.R., Abraham P.A., Marchi E., Limmathurotsakul D., Chantratita N.A., West T.E., Gharib S.A., Cliff J.M., Day N.P.J., Klenerman P., Dunachie S.J. Association of Diabetes Mellitus With a Shared Hyperinflammatory Immune Response in Patients With Melioidosis and Patients With Tuberculosis: An Observational Case-Control Study. Open Forum Infectious Diseases Vol.13 No.6 (2026). doi:10.1093/ofid/ofag286 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/117509
Title
Association of Diabetes Mellitus With a Shared Hyperinflammatory Immune Response in Patients With Melioidosis and Patients With Tuberculosis: An Observational Case-Control Study
Author's Affiliation
University of Washington
University of Washington School of Medicine
London School of Hygiene & Tropical Medicine
Mahidol University
Nuffield Department of Medicine
NIHR Oxford Biomedical Research Centre
Mahidol Oxford Tropical Medicine Research Unit
Bangladesh Medical University
Sunpasitthiprasong Hospital
University of Washington School of Medicine
London School of Hygiene & Tropical Medicine
Mahidol University
Nuffield Department of Medicine
NIHR Oxford Biomedical Research Centre
Mahidol Oxford Tropical Medicine Research Unit
Bangladesh Medical University
Sunpasitthiprasong Hospital
Corresponding Author(s)
Other Contributor(s)
Abstract
Background: Melioidosis is a serious infection caused by the bacterium Burkholderia pseudomallei with a case fatality rate of up to 40% in Northeast Thailand. Diabetes mellitus (DM) increases the risk of developing melioidosis by 12-fold. A similar, but less marked relationship with DM is seen in patients with tuberculosis, with a 3-fold increased risk of developing tuberculosis in people with DM. However, the mechanisms underlying the impact of DM on infection are not fully understood. Methods: Eighty-one patients with acute melioidosis from Northeast Thailand and 151 patients with tuberculosis from South Africa, Indonesia, Romania, and Peru, along with uninfected control cohorts, were studied by whole-blood RNA sequencing. Both supervised and unsupervised data analysis approaches, were performed including differential gene expression, pathway, and weighted gene coexpression network analyses. Results: DM status was associated with a hyperinflammatory response to both melioidosis and tuberculosis, with increased neutrophil and platelet degranulation and exaggerated activation of coagulation and scavenger activation pathways, along with decreased phosphoinositide 3-kinase protein kinase B signaling. In melioidosis, changes with DM were subtle but also included increased tumor necrosis factor signaling via nuclear factor κB and enhancement of endoplasmic reticulum stress and unfolded protein responses. DM-related changes were more distinct in tuberculosis, with marked reduction of interferon signaling responses. Conclusions: DM is associated with enhanced nonspecific inflammatory responses in both melioidosis and tuberculosis and an impaired interferon-mediated response to tuberculosis, with implications for future host-directed therapies.