Adrenal hormones mediate disease tolerance in malaria

Leen Vandermosten, Thao-Thy Pham, Sofie Knoops, Charlotte De Geest, Natacha Lays, Kristof Van der Molen, Christopher J. Kenyon, Manu Verma, Karen E. Chapman, Frans Schuit, Karolien De Bosscher, Ghislain Opdenakker and Philippe E. Van den Steen ()
Additional contact information
Leen Vandermosten: Rega Institute for Medical Research, KU Leuven
Thao-Thy Pham: Rega Institute for Medical Research, KU Leuven
Sofie Knoops: Rega Institute for Medical Research, KU Leuven
Charlotte De Geest: Rega Institute for Medical Research, KU Leuven
Natacha Lays: Rega Institute for Medical Research, KU Leuven
Kristof Van der Molen: Rega Institute for Medical Research, KU Leuven
Christopher J. Kenyon: The Queen’s Medical Research Institute, University of Edinburgh
Manu Verma: The Queen’s Medical Research Institute, University of Edinburgh
Karen E. Chapman: The Queen’s Medical Research Institute, University of Edinburgh
Frans Schuit: KU Leuven
Karolien De Bosscher: Ghent University
Ghislain Opdenakker: Rega Institute for Medical Research, KU Leuven
Philippe E. Van den Steen: Rega Institute for Medical Research, KU Leuven

Nature Communications, 2018, vol. 9, issue 1, 1-18

Abstract: Abstract Malaria reduces host fitness and survival by pathogen-mediated damage and inflammation. Disease tolerance mechanisms counter these negative effects without decreasing pathogen load. Here, we demonstrate that in four different mouse models of malaria, adrenal hormones confer disease tolerance and protect against early death, independently of parasitemia. Surprisingly, adrenalectomy differentially affects malaria-induced inflammation by increasing circulating cytokines and inflammation in the brain but not in the liver or lung. Furthermore, without affecting the transcription of hepatic gluconeogenic enzymes, adrenalectomy causes exhaustion of hepatic glycogen and insulin-independent lethal hypoglycemia upon infection. This hypoglycemia is not prevented by glucose administration or TNF-α neutralization. In contrast, treatment with a synthetic glucocorticoid (dexamethasone) prevents the hypoglycemia, lowers cerebral cytokine expression and increases survival rates. Overall, we conclude that in malaria, adrenal hormones do not protect against lung and liver inflammation. Instead, they prevent excessive systemic and brain inflammation and severe hypoglycemia, thereby contributing to tolerance.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-06986-5 Abstract (text/html)

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:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06986-5

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

DOI: 10.1038/s41467-018-06986-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

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