Regulation of iron metabolism in different bacterial infections
Year: 2015
Type: dissertation
Abstract: Iron is found in almost all living organisms, playing a central role in host-pathogen interactions and being crucial for both host and pathogens. In the host, iron is a crucial element, since it plays a key role in biological processes such as oxygen transport, biosynthesis of DNA, energy production and regulation of gene expression. However, high concentrations of iron can also be toxic to cells due to the ability to generate hydroxyl radicals. Thus, vertebrates developed proteins to transport and store iron: transferrin and ferritin, respectivetly. Hepcidin is a key protein of iron metabolism, since it binds to ferroportin, the iron exporter, regulating the release of iron to the serum. On the other hand, iron is also fundamental for pathogens that required it to its growth and proliferation, to the expression of virulence factors and to metabolic processes. Thereby, during infection, the host and the pathogen compete by this metal. Pathogens developed multiple strategies to acquire iron from the host during infection. Thus, making iron unavailable for microorganisms is a central mechanism in host defense. In this work, we investigated the regulation of iron metabolism in host during infection with Listeria monocytogenes, a gram-positive bacterium and Salmonella Typhimurium, a gram-negative bacterium in order to verify whether there are alterations in host iron metabolism depending of infection type and if hepcidin have a central role in these alterations. C57BL6 male mice were infected with 104 CFU of L. monocytogenes, S. Typhimurium, or an equivalent volume of vehicle and sacrificed at different time points. Bacterial load quantification, non-heme iron determination in liver, evaluation of iron distribution in tissue, histopathologic analyses and the expression of genes related with iron metabolism were analyzed. Our results show that in both infections with L. monocytogenes and S. Typhimurium the host immune system are not able to irradiate the infection and, thus, the bacterial load increases during the experiment. Regarding the hematological and serological parameters, a reduction of red blood cells and hematocrit is observed, as well as, of serum iron levels. The levels of interleukin-6 and hepcidin increase at different time points in each infection. Additionally, non-heme iron concentration increases in liver during infection with both pathogens. Histopathological alterations were also detected during infection with L monocytogenes and S. Typhimurium. Our data suggests that both infections induce alterations in host iron metabolism. However, the infection with S. Typhimurium appears to have earlier and more severe effects in the host than infection with L. monocytogenes.
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2890031118