Bacterial siderophores hijack neutrophil functions

Piu Saha, Beng San Yeoh, Rodrigo A. Olvera, Xia Xiao, Vishal Singh, Deepika Awasthi, Bhagawat C. Subramanian, Qiuyan Chen, Madhu Dikshit, Yanming Wang, Carole A. Parent, Matam Vijay-Kumar

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Neutrophils are the primary immune cells that respond to inflammation and combat microbial transgression. To thrive, the bacteria residing in their mammalian host have to withstand the antibactericidal responses of neutrophils.We report that enterobactin (Ent), a catecholate siderophore expressed by Escherichia coli, inhibited PMA-induced generation of reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) in mouse and human neutrophils. Ent also impaired the degranulation of primary granules and inhibited phagocytosis and bactericidal activity of neutrophils, without affecting their migration and chemotaxis. Molecular analysis revealed that Ent can chelate intracellular labile iron that is required for neutrophil oxidative responses. Other siderophores (pyoverdine, ferrichrome, deferoxamine) likewise inhibited ROS and NETs in neutrophils, thus indicating that the chelation of iron may largely explain their inhibitory effects. To counter iron theft by Ent, neutrophils rely on the siderophorebinding protein lipocalin 2 (Lcn2) in a "tug-of-war" for iron. The inhibition of neutrophil ROS and NETs by Ent was augmented in Lcn2-deficient neutrophils compared with wild-type neutrophils but was rescued by the exogenous addition of recombinant Lcn2. Taken together, our findings illustrate the novel concept that microbial siderophore's iron-scavenging property may serve as an antiradical defense system that neutralizes the immune functions of neutrophils.

Original languageEnglish (US)
Pages (from-to)4293-4303
Number of pages11
JournalJournal of Immunology
Volume198
Issue number11
DOIs
StatePublished - Jun 1 2017

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Saha, P., Yeoh, B. S., Olvera, R. A., Xiao, X., Singh, V., Awasthi, D., Subramanian, B. C., Chen, Q., Dikshit, M., Wang, Y., Parent, C. A., & Vijay-Kumar, M. (2017). Bacterial siderophores hijack neutrophil functions. Journal of Immunology, 198(11), 4293-4303. https://doi.org/10.4049/jimmunol.1700261