Association of Diabetes Mellitus With a Shared Hyperinflammatory Immune Response in Patients With Melioidosis and Patients With Tuberculosis: An Observational Case-Control Study

Journal article

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.

Authors: Rongkard, P; Kronsteiner, B; Eckold, C; Chamnan, P; Chumseng, S

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Oxford University Press
• Journal: Open Forum Infectious Diseases
• Volume: 13
• Issue: 6
• Article number: ofag286
• Publication date: 2026-06-17
• Acceptance date: 2026-04-30
• DOI: 10.1093/ofid/ofag286
• EISSN: 2328-8957
• ISSN: 2328-8957
• Language: English
• Keywords: diabetes mellitus; tuberculosis; transcriptome; melioidosis; host-pathogen response