Darwinian competition between different fetal precursors in tissue resident macrophage development
Tissue-resident macrophages (MΦTR) originate from fetal precursors. The relative potential of fetal precursors in determining development and functional capacity of MΦTR remains unclear. A recent "The EMBO Journal" paper by the Kopf group (IMHS) revealed the underlying molecular mechanism.
Every organ harbors a subset of tissue-resident macrophages (MΦTR) with distinct tissue-adapted functions. MΦTR develop during embryogenesis from so-called erythroid myeloid precursors that arise in the yolk sac in two waves with a first resulting in primitive MΦTR precursors and the second migrating to and differentiating in the fetal liver into fetal monocytes. We have studied development of lung resident alveolar macrophages (AM), to define the potential of the different MΦTR precursors in MΦTR development in general. By transplantation of different MΦTR precursors to newborns of a mouse strain lacking endogenous AM, we show that primitive MΦTR precursors are outcompeted and replaced by fetal monocytes in the lung during the third trimester of embryogenesis due to increased metabolic fitness and repression of transcription factors that drive differentiation. The data also reveal that AM derived from fetal monocytes have a superior functional capacity and protect mice from lung failure after influenza infection.
Link to the publication in external page "The EMBO Journal ".