Projects per year
Abstract
Immunity to malaria is often considered slow to develop but this only applies to defense mechanisms that function to eliminate parasites (resistance). In contrast, immunity to severe disease can be acquired quickly and without the need for improved pathogen control (tolerance). Using Plasmodium chabaudi we show that a single malaria episode is sufficient to induce host adaptations that can minimise inflammation, prevent tissue damage and avert endothelium activation, a hallmark of severe disease. Importantly, monocytes are functionally reprogrammed to prevent their differentiation into inflammatory macrophages and instead promote mechanisms of stress tolerance to protect their niche. This alternative fate is not underpinned by epigenetic reprogramming of bone marrow progenitors but appears to be imprinted within the remodelled spleen. Crucially, all of these adaptations operate independently of pathogen load and limit the damage caused by malaria parasites in subsequent infections. Acquired immunity to malaria therefore prioritises host fitness over pathogen clearance.
Original language | English |
---|---|
Article number | e63838 |
Number of pages | 33 |
Journal | eLIFE |
Volume | 10 |
DOIs | |
Publication status | Published - 23 Mar 2021 |
Keywords / Materials (for Non-textual outputs)
- disease tolerance
- acquired immunity
- malaria
- monocytes
- macrophages
- innate memory
- epigenetic reprogramming
- tissue niche
Fingerprint
Dive into the research topics of 'Inducible mechanisms of disease tolerance provide an alternative strategy of acquired immunity to malaria'. Together they form a unique fingerprint.Projects
- 3 Finished
-
-
Future-Proofing the sustainability of the MRC high throughput sequencing hub in Scotland
Blaxter, M.
1/10/12 → 30/09/14
Project: Research
-
NERC Support for the Ion Microprobe Facility at the University of Edinburgh
Craven, J., Harley, S. & Wood, R.
1/04/08 → 31/03/18
Project: Research