Organ-Specific Fate, Recruitment, and Refilling Dynamics of Tissue-Resident Macrophages during Blood-Stage Malaria

• Published in: Cell reports (Cambridge) Vol. 25; no. 11; pp. 3099 - 3109.e3
• Main Authors: Lai, Si Min, Sheng, Jianpeng, Gupta, Pravesh, Renia, Laurent, Duan, Kaibo, Zolezzi, Francesca, Karjalainen, Klaus, Newell, Evan W., Ruedl, Christiane
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.12.2018; Elsevier
• Subjects: alveolar macrophages; fetal; Kupffer cells; malaria; monocytes; niche; replenishment; self-renewal; tissue-resident macrophages; turnover; monocytes; replenishment; Kupffer cells; alveolar macrophages; tissue-resident macrophages; niche; malaria; turnover; self-renewal; fetal
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2018.11.059

Inflammation-induced disappearance of tissue-resident macrophages represents a key pathogen defense mechanism. Using a model of systemic blood-stage malaria, we studied the dynamics of tissue-resident macrophages in multiple organs to determine how they are depleted and refilled during the course of disease. We show that Plasmodium infection results in a transient loss of embryonically established resident macrophages prior to the parasitemia peak. Fate-mapping analysis reveals that inflammatory monocytes contribute to the repopulation of the emptied niches of splenic red pulp macrophages and hepatic Kupffer cells, while lung alveolar macrophages refill their niche predominantly through self-renewal. Interestingly, the local microenvironment of the spleen and liver can “imprint” the molecular characteristics of fetal-derived macrophages on newly differentiated bone marrow-derived immigrants with remarkably similar gene expression profiles and turnover kinetics. Thus, the mononuclear phagocytic system has developed distinct but effective tissue-specific strategies to replenish emptied niches to guarantee the functional integrity of the system. [Display omitted] •Loss of embryonically established resident macrophages during malaria•Inflammatory monocytes replenish spleen and liver F4/80hi macrophages•Alveolar macrophages refill their numbers by self-renewal•Post-entry monocytes gain the characteristics of fetal-derived macrophages Plasmodium infection leads to partial depletion of the resident macrophage population. Here, Lai et al. demonstrate that liver and spleen macrophages can be refilled by inflammatory monocytes following macrophage depletion, whereas the alveolar macrophage compartment is not accessible to external cell replenishment and regains its original numbers through self-renewal.