Role of Divalent Cations in Infections in Host-Pathogen Interaction

• Published in: International journal of molecular sciences 2024-09, Vol.25 (18), p.9775
• Main Authors: D'Elia, John A, Weinrauch, Larry A
• Format: Article
• Language: English
• Subjects: Alfacalcidol; Animals; Antibiotics; antimicrobial defense; Apoptosis; Autophagy; Cadmium; Calcifediol; Calcitonin; Calcium - metabolism; calcium ion channels; Cation Transport Proteins - metabolism; Cations; Cations, Divalent - metabolism; Creatinine; Development and progression; Diabetes; divalent cations; Health aspects; Host-parasite relationships; Host-Pathogen Interactions; Humans; Hypercalcemia; Immune response; Infection; Magnesium; Metabolism; microbial defense; Mutation; Mycobacterium tuberculosis - metabolism; Mycobacterium tuberculosis - pathogenicity; Parasites; Parathyroid hormone; Pathogens; Physiological aspects; Review; Tuberculosis; Tuberculosis - immunology; Tuberculosis - metabolism; Tuberculosis - microbiology; Vitamin D
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25189775

With increasing numbers of patients worldwide diagnosed with diabetes mellitus, renal disease, and iatrogenic immune deficiencies, an increased understanding of the role of electrolyte interactions in mitigating pathogen virulence is necessary. The levels of divalent cations affect host susceptibility and pathogen survival in persons with relative immune insufficiency. For instance, when host cellular levels of calcium are high compared to magnesium, this relationship contributes to insulin resistance and triples the risk of clinical tuberculosis. The movement of divalent cations within intracellular spaces contributes to the host defense, causing apoptosis or autophagy of the pathogen. The control of divalent cation flow is dependent in part upon the mammalian natural resistance-associated macrophage protein (NRAMP) in the host. Survival of pathogens such as within the bronchoalveolar macrophage is also dependent upon NRAMP. Pathogens evolve mutations to control the movement of calcium through external and internal channels. The host NRAMP as a metal transporter competes for divalent cations with the pathogen NRAMP in (whether in latent, dormant, or active phase). This review paper summarizes mechanisms of pathogen offense and patient defense using inflow and efflux through divalent cation channels under the influence of parathyroid hormone vitamin D and calcitonin.