Figure 7. Monocytes are transcriptionally reprogrammed in the remodelled spleen.
(A) RNA sequencing of spleen monocytes flow-sorted from AJ-infected mice (7 and 40 days p.i. for acute and chronic, respectively), once-infected mice (memory, 70 days p.i.), and reinfected mice (acute, 7 days p.i.). The heatmap shows all 111 differentially expressed genes in once-infected mice (DEG, relative to uninfected controls, padj <0.01, >1.5-fold change). (B) GO analysis of DEG in spleen monocytes during first infection (7 days p.i.), memory phase (70 days p.i.) and second infection (7 days p.i.). Mice were infected with P. chabaudi AJ and the top GO terms in once-infected mice are shown. (C) Working model of disease tolerance in malaria, showing the major changes in the myeloid compartment throughout chronic infection, convalescence and reinfection. Note that in the memory phase (one month after drug cure) there is no evidence that monocytes are epigenetically reprogrammed in the bone marrow but they are transcriptionally reprogrammed in the spleen. We therefore propose that the remodelled spleen imprints monocytes with tissue protective functions. In (A and B) n = 5–6 for infected mice and n = 6–7 for uninfected controls. (C) Icons credit: https://thenounproject.com/.
Figure 7—figure supplement 1. Tissue printing shapes the transcriptional programme of recruited monocytes to meet the needs of the niche.
