Kratofil, Rachel M. and Shim, Hanjoo B. and Shim, Raymond and Lee, Woo Yong and Labit, Elodie and Sinha, Sarthak and Keenan, Catherine M. and Surewaard, Bas G. J. and Noh, Ji Yeon and Sun, Yuxiang and Sharkey, Keith A. and Mack, Matthias and Biernaskie, Jeff and Deniset, Justin F. and Kubes, Paul (2022) A monocyte-leptin-angiogenesis pathway critical for repair post-infection. NATURE, 609 (7925). 166-+. ISSN 0028-0836, 1476-4687
Full text not available from this repository. (Request a copy)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 controll(1,2). Here, using a foreign body coated with Staphylococcus aureus and imaging overtime 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 function(3), 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VIRULENCE DETERMINANTS; CCR2(+) MONOCYTES; SKIN; MACROPHAGES; INFECTION; RECRUITMENT; EXPRESSION; GHRELIN; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 31 Jan 2024 15:01 |
| Last Modified: | 31 Jan 2024 15:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58560 |
Actions (login required)
 |
View Item |
