Function of Tissue Resident Macrophages
Depending on their origin, tissue macrophages can be classified as monocytic and embryonic origin in the steady state. Although the ontogeny of tissue macrophages has been extensively studied in recent years, the function of macrophage subsets of different origin in disease conditions has not been studied. We found that visceral adipose tissue (VAT) of humans and mice contained two distinct subsets of macrophages: CX3CR1+ CCR2+ and CX3CR1– CCR2–. Genetic fate mapping and parabiosis experiments revealed that these macrophage subsets were monocyte-derived and tissue resident, respectively. CX3CR1– CCR2– macrophages were derived from progenitors present on the day of birth. CX3CR1+ CCR2+ macrophages had transcriptome profile similar to circulating monocytes and were highly inflammatory compared to CX3CR1– CCR2– VAT resident macrophages. In patients and mice with myocardial infarction (MI), de novo insulin resistance was associated with gradual loss of VAT resident macrophages and infiltration of pro-inflammatory monocyte-derived macrophages. Depletion of monocyte-derived macrophages improved glucose tolerance after MI. We observed that declined systemic levels of macrophage-colony stimulating factor (M-CSF) after MI induced apoptosis in VAT resident but not monocyte-derived macrophages. M-CSF infusion after MI restored VAT resident macrophage number and improved glucose tolerance. Furthermore, VAT resident macrophages expressed high levels of the receptor for M-CSF (M-CSFR). Depletion of VAT resident macrophages and genetic deficiency in M-CSFR in myeloid cells exacerbated insulin resistance after MI. Taken together, our study demonstrates that macrophage subsets of two different origins, albeit residing in the same microenvironment, execute opposing functions in disease pathogenesis.
Vasamsetti SB, Coppin E, Zhang X, Florentin J, Koul S, Gotberg M, Clugston AS, Thoma F, Sembrat J, Bullock GC, Kostka D, St. Croix CM, Chattopadhyay A, Rojas M, Mulukutla S, Dutta P. Apoptosis of hematopoietic progenitor-derived adipose tissue resident macrophages contributes to insulin resistance after myocardial infarction. Sci Trans Med, 2020. PMCID: PMC7813555