The Tissue Macrophage Lineage

Despite accumulating evidence suggesting local self-maintenance of tissue macrophages in the steady state, the dogma remains that tissue macrophages derive from monocytes. In this presentation, I will discuss parabiosis, fate mapping, and adoptive transfer approaches that we developed in the laboratory to assess the contribution of monocytes to tissue resident macrophages in the steady state and after cell turnover. Using these approaches we found that monocytes contribute minimally to tissue resident macrophages in the steady state. Similarly, we found that after depletion of lung macrophages, the majority of repopulation occurs by local proliferation in a Csf-1 and Csf-2 dependent manner. This repopulation from a non-circulating population was stochastic and observed in both infection- and inflammatory-induced cytotoxicity of local macrophages. We also found that after bone marrow transplantation, host tissue macrophages retain the capacity to expand when the development of donor tissue macrophages is compromised. These results are consistent with recent results obtained in humans showing that macrophages can form in the absence of circulating monocytes. Collectively, these results indicate that tissue resident macrophages and circulating monocytes should be classified as independent mononuclear phagocyte lineages.