Diabetes impairs IFNγ-dependent antibacterial defense in the lungs

Diabetes mellitus is associated with an increased risk of pneumonia, often caused by so-called typical and atypical pathogens including Streptoccocus pneumoniae and Legionella pneumophila, respectively. Here, we employed a variety of mouse models to investigate how diabetes influences pulmonary antibacterial immunity. Following intranasal infection with S. pneumoniae or L. pneumophila, type 2 diabetic and prediabetic mice exhibited higher bacterial loads in their lungs compared to control animals. Single cell RNA sequencing, flow cytometry, and functional analyses revealed a compromised IFNγ production by natural killer cells in diabetic and prediabetic mice, which was associated with reduced IL-12 production by CD103