Neutrophil gelatinase-associated lipocalin and interleukin-10 regulate intramacrophage Chlamydia pneumoniae replication by modulating intracellular iron homeostasis

Infection with Chlamydiae ex vivo and in vivo revealed a significantly higher bacterial growth in peritoneal macrophages of Lcn-2 −/− than of wildtype mice. These differences were significantly more pronounced upon iron challenge, which stimulated bacterial growth. Accordingly, treatment with an anti-Lnc-2 antibody increased whereas addition of recombinant Lcn-2 reduced bacterial growth in infected macrophages. When investigating the underlying mechanisms we observed partly different expression of several iron metabolism genes between Lcn-2 +/+ and Lcn-2 −/− macrophages and most strikingly an increased formation of the anti-inflammatory cytokine IL-10 by Lcn-2 −/− macrophages. Upon treatment with an anti-IL10 antibody we experienced a significant increase of Chlamydial growth within Lcn-2 −/− macrophages along with a reduction of the major iron storage protein ferritin. Herein we provide first time evidence that Lcn-2 is involved in host defence against Chlamydia presumably by limiting the availability of iron to the pathogen. In the absence of Lcn-2, increased formation of IL-10 exerts protective effects by increasing the intracellular formation of ferritin, thereby reducing the access of iron for bacteria.