Question

Consider the following:

“Iron deficiency is the most common nutrient deficiency worldwide and routine supplementation is standard policy for pregnant mothers and children in most low-income countries. However, iron lies at the center of host-pathogen competition for nutritional resources and recent trials of iron administration in African and Asian children have resulted in significant excesses of serious adverse events including hospitalizations and deaths. Increased rates of malaria, respiratory infections, severe diarrhea and febrile illnesses of unknown origin have all been reported, but the mechanisms are unclear.”

Source: Cross et al. Oral iron acutely elevates bacterial growth in human serum. Scientific Reports , volume5, Article number: 16670 (2015)

Explain why iron supplementation can be associated with infectious disease.

Why is iron so important to both host cells and pathogens?

Answer 1

I will answer second question first for better understanding.

2. As we all know iron is required for humans as it is required to carry oxygen molecule which is essential in respiration. Iron deficiency impairs cell proliferation and immune function. Excess of Iron is also detrimental due to absence of iron excretory pathway.Hence, cellular homeostatic mechanisms balances needs and redox utility. In case of pathogen, iron redoxing enzymes are important for respiration, DNA synthesis, and free radical-scavenging mechanisms in bacteria.

1. Bacteria can acquire iron from transferrin, ferritin, and heme (eg Mycobacterium tuberculosis, Salmonella, and Listeria species). Bacteria synthesize high iron affinity compound like siderophores which takes iron from iron-binding proteins. It can also directly capture iron from iron binding proteins and heme at the bacterial cell membrane. pH of environment and oxidation reduction potential determines the binding of iron to transferrin. Due to infection, hypoxia is observed along with change in pH and oxidation-reduction potential. It is observed that the haptoglobin 2-2 polymorphism is associated with increased macrophagal iron, thus increased death risk. It is also observed that iron overload leads to inhibition of IFN-gamma, TNF-alpha, IL-12, and nitric oxide formation. It also impairs macrophage, neutrophil, and T-cell function. Thus immunity is further impaired.

All these mechanism helps pathogens for their survival, and host is unable to maintain the iron balance.