Dual roles of the bacterial siderophore enterobactin by inducing apoptosis in macrophages and promoting survival advantages to Salmonella typhimurium

• Published in: The Journal of immunology (1950) 2018-05, Vol.200 (1_Supplement), p.114-114.3
• Main Authors: Saha, Piu, Xiao, Xia, Yeoh, Beng San, Chen, Qiuyan, Katkere, Bhuvana, Kirimanjeswara, Girish Soorappa, Vijay-Kumar, Matam
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.200.Supp.114.3

Iron, an essential transition metal ion, is required to facilitate the antimicrobial and redox activity of heme proteins expressed in macrophages (Mφs). In this study, we investigated whether the chelation of iron by enterobactin (Ent; a prototypical bacterial siderophore) can affect the immune responses of macrophages. Herein, we demonstrated that exogenous Ent confers protection to the intracellular pathogen Salmonella enterica serovar Typhimurium from Mφs by promoting M1 to M2 polarization, reducing the expression of pro-inflammatory cytokines and impairing their intracellular killing. Accordingly, WT Salmonella survived better compared to Ent-deficient strain (ΔentB) in Mφs. The addition of apo-Ent (iron-free), but not ferric-Ent, rescued both strains, thus suggesting that the immuno-modulatory effect of Ent could be likely mediated via chelation of Mφs cellular iron. To determine whether the effects of Ent on Mφs could be due to altered cell viability, we next assessed the Mφs for markers of apoptosis via flow cytometry. Interestingly, we observed that apo-Ent, but not ferric-Ent, promoted a time-dependent apoptosis in Mφs, which can be detected as early as 12h after Ent treatment. These findings corroborated with the time-dependent release of lactate dehydrogenase (cytotoxicity marker) from Ent-treated Mφs. Collectively, our findings demonstrate that Ent not only facilitates bacterial iron uptake but also serves to safeguard bacteria against Mφ innate immune responses, which could be mediated, in part, by inducing delayed cellular apoptosis.