Diabetes mellitus is associated with a shared hyper-inflammatory immune response in melioidosis and tuberculosis patients: an observational case-control study

Melioidosis is a serious infection caused by the bacterium Burkholderia pseudomallei (Bp) with a case fatality rate of up to 40% in Northeast Thailand. Diabetes increases the risk of developing melioidosis by 12-fold. A similar, but less marked, relationship with diabetes is seen in tuberculosis (TB) patients, with a 3-fold increased risk of developing TB in people with diabetes. However, the mechanisms underlying increased susceptibility are not fully understood. Whole blood samples of 81 acute melioidosis patients from Northeast Thailand and 151 TB patients from South Africa, Indonesia, Romania and Peru alongside uninfected control cohorts were studied by whole blood RNA sequencing. We identified that having diabetes is associated with a hyper-inflammatory response to both melioidosis and TB, with increased neutrophil and platelet degranulation, and exaggerated activation of coagulation and scavenger activation pathways. The impact is more subtle in melioidosis but pronounced in tuberculosis with stunted interferon responses