Low levels of Fe and Se with high IL-6/IL-10 likely influence nutritional immunity in tuberculosis patients

Abstract Tuberculosis (TB) patients present dysregulated immunity, iron metabolism and anaemia of inflammation. In this study, circulatory cytokines, trace metals, and iron-related proteins (hepcidin, ferroportin, transferrin, DMT1, Nramp1, ferritin, ceruloplasmin, hemojuvelin, aconitase, transferring receptor) were monitored in case (active tuberculosis patients: ATB) and control (non-tuberculosis: NTB and healthy) study populations (n=72, male, 42.94 mean age (16-83)). Using serum elemental and cytokine levels, a partial least square discriminate analysis model (PLS-DA) was built and variables with a VIP score of >0.6 were selected as important markers. A biosignature of IL-13, IL-12(p70), IFN-γ, IL-10, IL-5, IL-18, IL-4, Selenium, and Aluminium clustered ATB away from controls. Interestingly, low iron and selenium levels, while high copper and aluminum levels were observed in ATB subjects. All the important serum cytokines were positively correlated in ATB subjects. A low abundance of transferrin, ferroportin, and hemojuvelin, while higher ferritin and ceruloplasmin levels explained an altered iron metabolism in ATB subjects which partially resolved upon completion of treatment. Further, the identified biosignature in TB patients, that explained anemia of inflammation, along with perturbed iron homeostasis could be useful targets for the development of host-directed adjunct therapeutics.