Exposure to unmethylated CpG DNA reduces the risk of asthma in mice and humans. In Immunity, Bureau and colleagues show that CpG expands a population of lung interstitial macrophages previously known to constitutively produce interleukin 10 (IL-10) and to protect mice from asthma. Interstitial macrophages are Ly6CloCD64lo and produce IL-10 after stimulation with CpG and lipopolysaccharide. CpG protects mice from asthma induced by sensitization with various agents, and interstitial macrophages from CpG-treated mice can transfer protection in a manner dependent on IL-10. At steady-state, these interstitial macrophages are partially maintained by CCR2-dependent blood-derived monocytes. However, their CpG-induced expansion is independent of local proliferation, sustained by recruitment of monocytes from the spleen and independent of CCR2, CCL2, CCL5 and CCL9. IV

Immunity 46, 457–473 (2017)