Infection Regulates Pro-Resolving Mediators that Lower Antibiotic Requirements

DSpace/Manakin Repository

Infection Regulates Pro-Resolving Mediators that Lower Antibiotic Requirements

Citable link to this page


Title: Infection Regulates Pro-Resolving Mediators that Lower Antibiotic Requirements
Author: Chiang, Nan; Fredman, Gabrielle; Bäckhed, Fredrik; Oh, Sungwhan; Vickery, Thad; Schmidt, Birgitta A R; Serhan, Charles Nicholas

Note: Order does not necessarily reflect citation order of authors.

Citation: Chiang, Nan, Gabrielle Fredman, Fredrik Bäckhed, Sungwhan F. Oh, Thad Vickery, Birgitta A. Schmidt, and Charles N. Serhan. 2012. Infection regulates pro-resolving mediators that lower antibiotic requirements. Nature 484(7395): 524-528.
Full Text & Related Files:
Abstract: Underlying mechanisms for how bacterial infections contribute to active resolution of acute inflammation are unknown. Here, we performed exudate leukocyte trafficking and mediator-metabololipidomics of murine peritoneal Escherichia coli (E. coli) infections with temporal identification of pro-inflammatory (prostaglandins and leukotrienes) and specialized pro-resolving mediators (SPM). In self-resolving E. coli exudates (\(10^5\) CFU), the dominant SPM identified were resolvin (Rv) D5 and protectin D1 (PD1), which at 12 h were significantly greater than levels in exudates from higher titer E. coli (\(10^7\) CFU) challenged mice. Germ-free mice displayed endogenous RvD1 and PD1 levels higher than in conventional mice. RvD1 and RvD5 (ng/mouse) each reduced bacterial titers in blood and exudates, E. coli-induced hypothermia and increased survival, demonstrating the first actions of RvD5. With human polymorphonuclear neutrophils (PMN) and macrophages, RvD1, RvD5, and PD1 each directly enhanced phagocytosis of E. coli, and RvD5 counter-regulated a panel of pro-inflammatory genes, including NF-κB and TNF-α. RvD5 activated the RvD1 receptor, GPR32, to enhance phagocytosis. With self-limited E. coli infections, RvD1 and the antibiotic ciprofloxacin accelerated resolution, each shortening resolution intervals (Ri). Host-directed RvD1 actions enhanced ciprofloxacin’s therapeutic actions. In \(10^7\) CFU E. coli infections, SPM (RvD1, RvD5, PD1) together with ciprofloxacin also heightened host antimicrobial responses. In skin infections, SPM enhanced vancomycin clearance of Staphylococcus aureus. These results demonstrate that specific SPM are temporally and differentially regulated during infections and that they are anti-phlogistic, enhance containment and lower antibiotic requirements for bacterial clearance.
Published Version: doi:10.1038/nature11042
Other Sources:
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at
Citable link to this page:
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)


Search DASH

Advanced Search