Project description:Effective host defense against infection relies on the tight coordination of immune activation, metabolic adaptation, and redox control, yet how these processes are integrated remains incompletely understood. Here, we identify dipeptidyl peptidase 3 (Dpp3) as a negative regulator of antimicrobial immunity. Dpp3-/- mice exhibit enhanced resistance to Klebsiella pneumoniae infection, with reduced bacterial burden, preserved tissue integrity, and attenuated systemic inflammation. This response is associated with increased phagocytic activity, expansion of germinal centres and plasma cells, and elevated interferon-γ production by T cells. Mechanistically, Dpp3 deficiency leads to reduced Nrf2 protein levels upon stimulation, resulting in heightened ROS accumulation and amplified NF-κB signaling. Integrated metabolomic and transcriptomic analyses of Dpp3-/- immune cells reveal mitochondrial dysfunction and a shift toward biosynthetic and antioxidant-supportive metabolic programs. Collectively, our findings identify Dpp3 as a molecular brake on host defense and uncover a regulatory axis linking redox balance, immunometabolism, and inflammation during infection.
Project description:We performed Spatial transcriptomics (Visium) using the 10X Genomics platform to investigate the role of the autophagy-related protein ATG7 in the context of nontuberculous mycobacterial (NTM) infection. ATG7 in innate immune cells plays a critical role in controlling NTM infection and protecting lung tissue from pathological inflammation. This study represents single-cell analysis of Mice deletion of Atg7 in innate immune cells and reveals the importance of ATG7 in mediating antimicrobial responses during infection and its essential role in host defense mechanisms against NTM.
Project description:We performed single-cell RNA sequencing (scRNA-seq) using the 10X Genomics platform to investigate the role of the autophagy-related protein ATG7 in the context of nontuberculous mycobacterial (NTM) infection. ATG7 in innate immune cells plays a critical role in controlling NTM infection and protecting lung tissue from pathological inflammation. This study represents single-cell analysis of Mice deletion of Atg7 in innate immune cells and reveals the importance of ATG7 in mediating antimicrobial responses during infection and its essential role in host defense mechanisms against NTM.
