Yolk Sac Macrophages, Fetal Liver, and Adult Monocytes Can Colonize an Empty Niche and Develop into Functional Tissue-Resident Macrophages

Abstract

Tissue-resident macrophages can derive from yolk sac macrophages (YS-Macs), fetal liver monocytes (FL-MOs), or adult bone-marrow monocytes (BM-MOs). The relative capacity of these precursors to colonize a niche, self-maintain, and perform tissue-specific functions is unknown. We simultaneously transferred traceable YS-Macs, FL-MOs, and BM-MOs into the empty alveolar macrophage (AM) niche of neonatal Csf2rb(-/-) mice. All subsets produced AMs, but in competition preferential outgrowth of FL-MOs was observed, correlating with their superior granulocyte macrophage-colony stimulating factor (GM-CSF) reactivity and proliferation capacity. When transferred separately, however, all precursors efficiently colonized the alveolar niche and generated AMs that were transcriptionally almost identical, self-maintained, and durably prevented alveolar proteinosis. Mature liver, peritoneal, or colon macrophages could not efficiently colonize the empty AM niche, whereas mature AMs could. Thus, precursor origin does not affect the development of functional self-maintaining tissue-resident macrophages and the plasticity of the mononuclear phagocyte system is largest at the precursor stage.

Perinatal Activation of the Interleukin-33 Pathway Promotes Type 2 Immunity in the Developing Lung

“…We therefore investigated the concentration of IL-33 protein in lysed lung cells in steady state (PBS) or after administration of HDM to unsensitized mice. In steady state, IL-33 protein concentration peaked around PND14 ( Figure 4C; van de Laar et al, 2016). At 16 hr after the administration of HDM, the expression of IL-33 was significantly higher in lung cell homogenates of PND14 lungs compared to PND3 or adult lungs ( Figure 4C).…”

“…This alveolar phase of lung growth lasts until 3 years of age and is controlled by many growth factors and cytokines that could also influence (Schittny et al, 2008). Fetal lung is first populated around E12 by CD45 + yolk sac-derived macrophages (De Kleer et al, 2014;Guilliams et al, 2013;Schulz et al, 2012;van de Laar et al, 2016). We recently have shown that this first wave of yolk sac-derived macrophages is followed by a consecutive wave of fetal liver-derived monocytes that enter the lung around E18, the start of the saccular phase in mice, and give rise to alveolar macrophages (AM) under the influence of GM-CSF van de Laar et al, 2016).…”

“…Fetal lung is first populated around E12 by CD45 + yolk sac-derived macrophages (De Kleer et al, 2014;Guilliams et al, 2013;Schulz et al, 2012;van de Laar et al, 2016). We recently have shown that this first wave of yolk sac-derived macrophages is followed by a consecutive wave of fetal liver-derived monocytes that enter the lung around E18, the start of the saccular phase in mice, and give rise to alveolar macrophages (AM) under the influence of GM-CSF van de Laar et al, 2016). The prenatal influx of fetal liverderived monocytes was accompanied by a rapid influx of granulocytes that peaked in number at PND1 ( Figures 1A, 1B, and S1).…”

Human and murine splenic neutrophils are potent phagocytes of IgG-opsonized red blood cells

“…Indeed, there is a large body of evidence that AIHA can be induced by an underlying disease in the patient which may lower the threshold of the neutrophils to phagocytose IgG-opsonized RBCs, and thus exacerbate the hemolytic anemia. It is important to keep in mind that during these pathological conditions the cellular composition of the spleen can change 43,44 which subsequently may influence phagocytosis. Additionally, IV immunoglobulin administration, a common therapy in AIHA can change cellular distribution in the spleen which may affect erythrophagocytosis.…”

Exogenous remodeling of lung resident macrophages protects against infectious consequences of bone marrow-suppressive chemotherapy

“…5C). It should be noted that this protective effect was unexpected, because macrophages transferred into the lung, regardless of their origin, rapidly (within days) alter their phenotype (33,34). Overall, based on depletion (Fig.…”