Iron traffics in circulation bound to a siderocalin (Ngal)–catechol complex

Siderophores have also been identified in mammals.

“Rather, siderophores have also been identified in mammals (Bao et al., 2010;Devireddy et al., 2010).”

The discovery of putative mammalian siderophores suggests humans may maintain iron homeostasis using mechanisms similar to microbes.

“Finally, the discovery of putative mammalian siderophores suggests that humans might use mechanisms analogous to microbes to maintain iron homeostasis (Bao et al., 2010; Devireddy et al., 2010).”

Lcn2 may contribute to limiting M. tuberculosis by shuttling iron out of macrophages, which is supposed to result from binding of a mammalian siderophore.

“In addition, Lcn2 may contribute to this effect by shuttling iron out of macrophages, which is supposed to result from binding of a mammalian siderophore (211, 212).”

Higher organisms such as fungi or mammals are able of producing this type of iron-scavenging molecules.

“Interestingly, also higher organisms such as fungi or mammals are able of producing this type of iron-scavenging molecules [120,121,122].”

Lcn2 binds distinct types of siderophores, low molecular mass compounds with high affinity and specificity for ferric iron.

“Lcn2 binds distinct types of so-called siderophores, low molecular mass compounds with remarkably high affinity and specificity for ferric iron.”

Some mammalian siderophores such as catechols are probably synthesized from commensal metabolites or dietary precursors.

“While some of these compounds such as citrate are ubiquitous substrates, other mammalian siderophores such as catechols are probably synthesized from commensal metabolites or dietary precursors [11, 50, 252].”

Lcn2 delivers bacterial and mammalian siderophore-bound iron to the Lcn2 receptor on host cells, suggesting it modulates iron trafficking during infection.

“Lcn2 delivers bacterial as well as mammalian siderophore-bound Fe [131,132] to the Lcn2 receptor expressed by host cells, suggesting that it modulates Fe trafficking and hence Fe metabolism during infection (Fig 2).”

Mammalians produce catechol-like siderophores including 2,5-dihydroxybenzoic acid (2,5-DHBA).

“Siderophores are not limited to microbes as mammalians produce catechol like siderophore including, 2,5-dihydroxybenzoic acid (2,5-DHBA)”

Lcn2 binds siderophores such as enterobactin and delivers Lcn2-Fe-siderophore complexes to host cells through the Lcn2 receptor, blocking bacterial uptake of iron-laden siderophores.

“Lcn2 binds siderophores such as enterobactin and delivers Lcn2-Fe-siderophore complexes to host cells via the Lcn2 receptor (88, 89), inhibiting bacterial uptake of Fe-laden siderophores (87, 90).”