Inducible mechanisms of disease tolerance provide an alternative strategy of acquired immunity to malaria.

Disease tolerance is an important alternative strategy for rapidly acquired immunity to malaria. We show that tolerance is induced by a single malaria episode - in the absence of parasite clearance. Inflammatory spleen monocytes from C57Bl6/J mice with memory of malaria infection dramatically change their transcriptional response to a second infection; instead of driving emergency inflammation they promote stress and tissue tolerance (RNAseq data available in GEO series GSE150047). This unique functional profile is not underpinned by alterations in the epigenetic landscape of inflammatory monocytes before their release from the bone marrow (ChIPseq data available in GEO series GSE150478) - tolerance is therefore imprinted within the spleen (microarray data available in GEO series GSE149894). Hosts thus acquire long-lasting mechanisms that control inflammation (reducing collateral tissue damage) and learn to actively promote stress tolerance (protecting tissues against toxic products and processes) after one malaria episode. Refer to individual Series