Targeted labeling and depletion of alveolar macrophages using VeDTR mouse technology

Abstract

<h2>Summary</h2> Alveolar macrophages (AMs) are essential for maintaining lung homeostasis. However, their roles in respiratory infections have been controversial because the methods of depleting them have often suffered from poor cell selectivity. To resolve this problem, we here used VeDTR technology to generate a transgenic mouse line in which AMs can be specifically depleted using diphtheria toxin. When various respiratory infections were examined using this system, we found that AMs prevented the proliferation of <i>Mycobacterium abscessus</i>. This result differed from previous findings using clodronate liposomes to deplete macrophages. We also revealed that the disappearance of AMs contributes to the reduction of bacterial load in the lungs and that AMs are indispensable for GM-CSF-mediated defense against <i>M. abscessus</i> infection. Taken together, the development of an AM-specific depletion system has provided an opportunity to study the roles of AMs in various respiratory infections from a different perspective.