Immunosuppression of the host and delivery of iron to the pathogen: a possible dual role of siderophores in the pathogenesis of microbial infections?

Abstract

Iron is an essential growth factor for procaryotes as well as for eucaryotes. Microorganisms have developed specific iron-uptake systems by producing low-molecular weight iron-chelating compounds (siderophores). We have examined the effect of the siderophores desferrioxamine (DFO), desferrichrome (DFC), desferriaerobactin (DFAB) and desferrienterobactin (DFEA) on the mitogen-stimulated activation and proliferation of mouse T cells. The hydroxamate siderophores DFO, DFC and DFAB cause an immunosuppressive effect on T cells which is related to the iron complexation constant of the siderophores and can be reversed by equimolar ferric iron. In contrast, the catecholate siderophore DFEB and its ferrated derivative turned out to be cytotoxic for T cells. These results suggest a dual role of siderophores in the infectious process, i.e., growth enhancement of the invading pathogen and inhibition of the host immune defense.