Homeostatic vs inflammatory replenishment of tissue mononuclear phagocytes revealed by fate mapping CSF1R myeloid precursors

The myelopoeitic precursors in bone marrow give rise to an array of immune cells including monocytes, macrophages, dendritic cells and neutrophils/granulocytes. These cells are distributed throughout the body and perform a variety of functions including homeostatic regulation of tissue and responses to tissue damage or invading pathogens. The precursors for each of these cell types have been increasingly characterized and identified, however many precursor populations reveal pluripotent potential. We performed adoptive precursor transfer of cells sorted on their relative expression of the colony stimulating factor 1 receptor (Csf1r) using the Csf1r-eGFP transgenic mouse model and Gr-1 antibody reactivity and fate-mapped the differentiation of various precursor populations. We observed variability in retention and differentiation of these populations within the bone marrow following transfer into sub-lethally irradiated recipients. The differentiation potentials of the precursor cell populations were modulated by the relative marker expression at the time of transfer.

Csf1r+/Gr-1+ cells failed to populate the bone marrow during inflammatory conditions. Csf1r+/Gr-1- cell recipients revealed eGFP expression in tissue-resident cells marked with homeostatic and inflammatory markers in equal measure. This modulatory effect however was most apparent following transfer of the least differentiated Csf1r-/Gr-1- precursor. In which recipients revealed only homeostatic replenishment of eGFP+ tissue macrophages and dendritic cells despite competition from host-derived (non eGFP) ly-6C+ “inflammatory” monocytes. These data reveal that homeostatic and inflammatory population of tissues by MPS cells can occur via the same precursor population but by independent differentiation pathways. Competitive re-population of tissues occurred between donor derived mononuclear phagocytes and host derived “inflammatory” monocyte and tissue-resident populations. We observed extensive multi-potent potential in pre-Csf1r (pre eGFP) expressing myeloid precursors using eGFP expression to trace their progeny through to tissue-resident mononuclear phagocytes.