TY - JOUR TI - Inducible mechanisms of disease tolerance provide an alternative strategy of acquired immunity to malaria AU - Nahrendorf, Wiebke AU - Ivens, Alasdair AU - Spence, Philip J A2 - Ginhoux, Florent A2 - Rath, Satyajit VL - 10 PY - 2021 DA - 2021/03/23 SP - e63838 C1 - eLife 2021;10:e63838 DO - 10.7554/eLife.63838 UR - https://doi.org/10.7554/eLife.63838 AB - 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. KW - disease tolerance KW - malaria KW - monocytes KW - macrophages KW - innate memory KW - tissue niche JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -