Abstract

FR.02.05

Iron-withholding strategies in innate immunity: scavenging of microbial siderophores by Tear Lipocalin

Redl B. 
Division of Molecular Biology Biocenter-Innsbruck Medical University, Innsbruck, Austria

Iron is an essential element for microbial growth and upon infection iron acquisition is critical for pathogenicity. Invading pathogens respond to the low levels of free iron, normally found in the host, by the secretion of siderophores that have high affinity to usurp the limited level of host iron. However, recent investigations demonstrated the presence of siderophore scavenging proteins in mammals. They belong to the superfamily of lipocalins. One is NGAL (neutrophil gelatinase-associated lipocalin or lipocalin 2), which is highly produced by neutrophiles. The other is human tear lipocalin (TL, also known as lipocalin 1), which is a secretory protein present in large amounts in fluids that cover epithelial surfaces such as tears and respiratory secretions. It is supposed to act as a physiological scavenger of hydrophobic, potentially harmful molecules, and it is also known to inhibit bacterial growth. Our recent investigations demonstrated that it interferes with microbial growth by scavenging of siderophores, similar as described for NGAL. However, in contrast to NGAL, which has a high specificity for bacterial catecholate-type siderophores, TL binds to a broad array of siderophores, including bacterial catecholate-type enterobactin and hydroxamate-type desferrioxamineB, and all major classes of fungal siderophores. By adding exogenous TL, bacterial and fungal growth can be inhibited under iron-limiting conditions. Thus, TL might be a novel member of the innate immune system, especially involved in mucosal defense against fungal infections.

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