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

14 Citations (Scopus)

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

Fingerprint

Siderophores
Neutrophils
Enterobactin
Iron
Reactive Oxygen Species
Microbiological Phenomena
Ferrichrome
Theft
Deferoxamine
Chemotaxis
Phagocytosis
Immune System

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Saha, P., Yeoh, B. S., Olvera, R. A., Xiao, X., Singh, V., Awasthi, D., ... Kumar, M. V. (2017). Bacterial siderophores hijack neutrophil functions. Journal of Immunology, 198(11), 4293-4303. https://doi.org/10.4049/jimmunol.1700261
Saha, Piu ; Yeoh, Beng San ; Olvera, Rodrigo A. ; Xiao, Xia ; Singh, Vishal ; Awasthi, Deepika ; Subramanian, Bhagawat C. ; Chen, Qiuyan ; Dikshit, Madhu ; Wang, Yanming ; Parent, Carole A. ; Kumar, Matam Vijay. / Bacterial siderophores hijack neutrophil functions. In: Journal of Immunology. 2017 ; Vol. 198, No. 11. pp. 4293-4303.
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Saha, P, Yeoh, BS, Olvera, RA, Xiao, X, Singh, V, Awasthi, D, Subramanian, BC, Chen, Q, Dikshit, M, Wang, Y, Parent, CA & Kumar, MV 2017, 'Bacterial siderophores hijack neutrophil functions', Journal of Immunology, vol. 198, no. 11, pp. 4293-4303. https://doi.org/10.4049/jimmunol.1700261

Bacterial siderophores hijack neutrophil functions. / Saha, Piu; Yeoh, Beng San; Olvera, Rodrigo A.; Xiao, Xia; Singh, Vishal; Awasthi, Deepika; Subramanian, Bhagawat C.; Chen, Qiuyan; Dikshit, Madhu; Wang, Yanming; Parent, Carole A.; Kumar, Matam Vijay.

In: Journal of Immunology, Vol. 198, No. 11, 01.06.2017, p. 4293-4303.

Research output: Contribution to journalArticle

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AU - Saha, Piu

AU - Yeoh, Beng San

AU - Olvera, Rodrigo A.

AU - Xiao, Xia

AU - Singh, Vishal

AU - Awasthi, Deepika

AU - Subramanian, Bhagawat C.

AU - Chen, Qiuyan

AU - Dikshit, Madhu

AU - Wang, Yanming

AU - Parent, Carole A.

AU - Kumar, Matam Vijay

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Saha P, Yeoh BS, Olvera RA, Xiao X, Singh V, Awasthi D et al. Bacterial siderophores hijack neutrophil functions. Journal of Immunology. 2017 Jun 1;198(11):4293-4303. https://doi.org/10.4049/jimmunol.1700261