Distinct macrophage subpopulations characterize acute infection and chronic inflammatory lung disease

Although great progress has been made in delineating lung dendritic cell and lymphocyte subpopulations, similar advances in lung macrophages (M phi s) have been hampered by their intrinsic autofluorescence, cell plasticity, and the complexities of monocyte-Mphi compartmentalization. Using spectral scanning, we define alveolar Mphi autofluorescence characteristics, which has allowed us to develop an alternative flow cytometry method. Using this methodology, we show that mouse lung Mphis form distinct subpopulations during acute inflammation after challenge with LPS or influenza virus, and in chronic inflammatory lung disease consequent to SHIP-1 deletion. These subpopulations are distinguished by differential Mac-1 and CD11c integrin expression rather than classical M1 or M2 markers, and display differential gene signatures ex vivo. Whereas the resolution of acute inflammation is characterized by restoration to a homogenous population of CD11chighMac-1 neg/low Mphis reflective of lung homeostasis, chronic inflammatory lung disease associated with SHIP-1 deficiency is accompanied by an additional subpopulation of CD11chighMac-1pos Mphis that tracks with lung disease in susceptible genetic background SHIP-1-/- animals and disease induction in chimeric mice. These findings may help better understand the roles of Mphi subpopulations in lung homeostasis and disease