- Neutrophil myeloperoxidase diminishes the toxic effects and mortality induced by lipopolysaccharide
Reber et al. reveal a protective function for neutrophils after lethal endotoxin challenge using a novel mouse model of diphtheria toxin–inducible neutropenia. Neutrophil expression of myeloperoxidase (MPO) is necessary for this protection. These findings imply that neutrophils protect the host by limiting the extent of LPS-induced pathology in an MPO-dependent manner.
- Secretogranin III as a disease-associated ligand for antiangiogenic therapy of diabetic retinopathy
LeBlanc et al. uncover secretogranin III (Scg3) as a unique disease-associated vascular permeability and angiogenic factor using comparative ligandomics. Scg3-neutralizing antibodies alleviate vascular leakage in diabetic retinopathy mice and retinal neovascularization in oxygen-induced retinopathy mice with high efficacy.
- p38 inhibition provides anti–DNA virus immunity by regulation of USP21 phosphorylation and STING activation
Chen et al. show that USP21 is a deubiquitinating enzyme for the adaptor protein STING and that it negatively regulates the DNA virus–induced production of type I interferons. HSV-1 infection recruited USP21 to STING at a late stage by p38-mediated phosphorylation of USP21 at Ser538.
- Inflammatory monocytes require type I interferon receptor signaling to activate NK cells via IL-18 during a mucosal viral infection
Although type I interferon is critical for NK cell activation, the underlying mechanism is under debate and is unknown during a mucosal infection. Lee et al. have determined that type I interferon induces inflammatory monocytes to produce IL-18 to directly activate NK cells to combat viral infections.
- VEGF165-induced vascular permeability requires NRP1 for ABL-mediated SRC family kinase activation
Fantin et al. show that the VEGF isoform VEGF165 signals through a complex of VEGFR2 and NRP1, in which the NRP1 cytoplasmic domain promotes the ABL-mediated activation of SRC family kinases to evoke a hyperpermeability response, a known cause of pathological edema.
- Innate immunity to RNA virus is regulated by temporal and reversible sumoylation of RIG-I and MDA5
Hu et al. show that sumoylation of the viral RNA sensors RIG-I and MDA5 by TRIM38 in uninfected and early-infected cells, and their desumoylation by SENP2 in the late phase of infection, ensure efficient innate immune responses to RNA viruses and their timely termination upon resolution of infection.
- Myeloid-derived cullin 3 promotes STAT3 phosphorylation by inhibiting OGT expression and protects against intestinal inflammation
Li et al. show that OGT-mediated STAT3 O-GlcNAcylation, which is modulated by CUL3-Nrf2 signaling, negatively regulates STAT3 phosphorylation and IL-10 production in macrophages and exacerbates experimental colitis and colitis-associated cancer.
- Eros is a novel transmembrane protein that controls the phagocyte respiratory burst and is essential for innate immunity
Thomas et al. show that a novel protein, Eros, controls the abundance of components of the phagocyte NADPH oxidase, making it essential for the phagocyte respiratory burst and defense against common infections.