The effect of hepcidin on iron homeostasis.

<p>In the absence of hepcidin, iron absorbed from the diet by duodenal enterocytes is transported into the serum via ferroportin, and iron captured from senescent red blood cells is exported from splenic macrophages. In the presence of hepcidin, iron is retained in duodenal enterocytes, which eventually shed from the intestinal tract, blocking iron absorption from the diet. Mononuclear phagocytes retain and accumulate recycled iron rather than releasing it back into circulation, causing a drop in serum iron levels.</p

Mechanisms of hepcidin induction.

<p>In hepatocytes, hepcidin induction is mediated primarily by BMP ligands binding with the HJV/BMPR complex. BMP6 is induced by high iron levels via an undefined mechanism. The protease TMPRSS6 inhibits hepcidin production by degrading HJV in response to low iron levels [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004998#ppat.1004998.ref095" target="_blank">95</a>]. High holo-transferrin levels stabilize the transferrin receptor 2 (Tfr2)/HFE complex, which promotes hepcidin induction, possibly by direct binding with HJV or BMPR [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004998#ppat.1004998.ref100" target="_blank">100</a>]. Hepcidin can also be induced by IL-6 via STAT3 signaling in hepatocytes and myeloid leukocytes. Inflammation can stimulate hepcidin production in myeloid leukocytes through pathogen recognition receptor signaling and through autocrine and paracrine production of IL-6.</p

Overview of host iron homeostasis.

<p>Iron is absorbed from the diet by duodenal enterocytes and transported into the bloodstream, where it is bound by transferrin. Most iron is incorporated into erythrocytes for heme synthesis. Splenic macrophages recover iron from senescent erythrocytes and release iron into circulation via ferroportin. Smaller amounts of iron are imported into other tissues as needed. Iron loss is not directly regulated and occurs through minor bleeding and shedding of duodenal enterocytes. Approximate iron content of adult human tissues is represented in parentheses.</p

Summary of the role of hepcidin in specific infections.

<p>Hepcidin-mediated iron restriction is protective against some extracellular infections and potentially detrimental in host defense against pathogens that reside in the intracellular compartment. Hepcidin has complex effects in infection by <i>Plasmodium</i> species and HCV.</p

Additional file 1 of A computational model of invasive aspergillosis in the lung and the role of iron

Overview, Design Concepts, and Details (ODD) protocol for the agent-based model. A complete description of the agent-based model, including process ordering, state variable values, and algorithm pseudocode (in.pdf format). (PDF 145 kb

Additional file 2 of A computational model of invasive aspergillosis in the lung and the role of iron

State variables for the agent-based model. Descriptions and values for all state variable values, organized by cell type (with global variables indicated as such). N(μ,σ)indicates values taken from a normal distribution with mean μ and standard deviation σ (in.pdf format). (PDF 985 kb

Additional file 3 of A computational model of invasive aspergillosis in the lung and the role of iron

Experimental design and results of parameter sensitivity analysis. Parameters not validated by literature are altered to 10 %, 50 %, and 200 % of baseline values in order to determine the effect of each (one at a time). Relevant model dynamics are presented under both normal and neutropenic conditions (in.pdf format). (PDF 186 kb