A monocyte–leptin–angiogenesis pathway critical for repair post-infection

Rachel M. Kratofil, Hanjoo B. Shim, Raymond Shim, Woo Yong Lee, Elodie Labit, Sarthak Sinha, Catherine M. Keenan, Bas G. J. Surewaard, Ji Yeon Noh, Yuxiang Sun, Keith A. Sharkey, Matthias Mack, Jeff Biernaskie, Justin F. Deniset () and Paul Kubes ()
Additional contact information
Rachel M. Kratofil: University of Calgary
Hanjoo B. Shim: University of Calgary
Raymond Shim: University of Calgary
Woo Yong Lee: University of Calgary
Elodie Labit: University of Calgary
Sarthak Sinha: University of Calgary
Catherine M. Keenan: University of Calgary
Bas G. J. Surewaard: University of Calgary
Ji Yeon Noh: Texas A&M University
Yuxiang Sun: Texas A&M University
Keith A. Sharkey: University of Calgary
Matthias Mack: University Hospital Regensburg
Jeff Biernaskie: University of Calgary
Justin F. Deniset: University of Calgary
Paul Kubes: University of Calgary

Nature, 2022, vol. 609, issue 7925, 166-173

Abstract: Abstract During infection, inflammatory monocytes are thought to be key for bacterial eradication, but this is hard to reconcile with the large numbers of neutrophils that are recruited for each monocyte that migrates to the afflicted tissue, and the much more robust microbicidal functions of the neutrophils. However, unlike neutrophils, monocytes have the capacity to convert to situationally specific macrophages that may have critical functions beyond infection control1,2. Here, using a foreign body coated with Staphylococcus aureus and imaging over time from cutaneous infection to wound resolution, we show that monocytes and neutrophils are recruited in similar numbers with low-dose infection but not with high-dose infection, and form a localization pattern in which monocytes surround the infection site, whereas neutrophils infiltrate it. Monocytes did not contribute to bacterial clearance but converted to macrophages that persisted for weeks after infection, regulating hypodermal adipocyte expansion and production of the adipokine hormone leptin. In infected monocyte-deficient mice there was increased persistent hypodermis thickening and an elevated leptin level, which drove overgrowth of dysfunctional blood vasculature and delayed healing, with a thickened scar. Ghrelin, which opposes leptin function3, was produced locally by monocytes, and reduced vascular overgrowth and improved healing post-infection. In sum, we find that monocytes function as a cellular rheostat by regulating leptin levels and revascularization during wound repair.

Date: 2022
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-022-05044-x Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:609:y:2022:i:7925:d:10.1038_s41586-022-05044-x

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-022-05044-x

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().