March 2016 | Volume 213, No. 3
Brief Definitive Reports
- Antibodies against a secreted product of Staphylococcus aureus trigger phagocytic killing
Vaccines and antibody therapeutics targeting staphylococcal surface molecules have failed to achieve clinical efficacy against MRSA infection. Here, Thomer et al. show that the R domain of prothrombin directs fibrinogen to the surface of S. aureus, which generates a protective coat for the pathogen, inhibiting phagocytosis by immune cells. The use of R-specific antibodies allows for immune cell recognition and protects mice against lethal bloodstream infections by broad spectrum MRSA isolates.
- Mediator facilitates transcriptional activation and dynamic long-range contacts at the IgH locus during class switch recombination
Thomas-Claudepierre et al. report that mediator facilitates the long-range contacts between acceptor switch regions and the IgH locus enhancers during class switch recombination and their transcriptional activation.
- Strictly co-isogenic C57BL/6J-Prnp−/− mice: A rigorous resource for prion science
Nuvolone et al. report a new mouse model to elucidate the functional role of cellular prion protein in physiology and disease.
- RNase H2 catalytic core Aicardi-Goutières syndrome–related mutant invokes cGAS–STING innate immune-sensing pathway in mice
Mice with a mutated form of RNase H2 found in patients with the neuroinflammatory Aicardi-Goutières Syndrome develop a lethal, cGAS–STING–dependent disease.
- The glycolytic enzyme PKM2 bridges metabolic and inflammatory dysfunction in coronary artery disease
Shirai et al. show that the glycolytic enzyme PKM2 serves as a molecular integrator of metabolic dysfunction, oxidative stress and tissue inflammation in macrophages from patients with atherosclerotic coronary artery disease.
- Intestinal microbiota sustains inflammation and autoimmunity induced by hypomorphic RAG defects
Rigoni et al. report that hypomorphic Rag2R229Q mutation is associated with altered microbiota composition and defects in the gut–blood barrier and suggest that intestinal microbes may play a critical role in the distinctive immune dysregulation of Omenn syndrome.
- Otud7b facilitates T cell activation and inflammatory responses by regulating Zap70 ubiquitination
Hu et al. demonstrate that the deubiquitinase Otud7b acts as a positive regulator of TCR-proximal signaling and T cell activation by deubiquitinating Zap70.
- Leukemia-associated activating mutation of Flt3 expands dendritic cells and alters T cell responses
Lau et al. show that the FLT3-ITD mutation directly affects dendritic cell development in preleukemic mice, indirectly modulating T cell homeostasis and supporting the expansion of regulatory T cells.
- Functional screen identifies regulators of murine hematopoietic stem cell repopulation
Holmfeldt et al. perform a transplant-based screen to identify regulators of HSPC engraftment and report that Foxa3 is critical for optimal HSC function after transplant.
- Integrin β3 inhibition is a therapeutic strategy for supravalvular aortic stenosis
Misra et al. elucidate the origin of smooth muscle cells involved in supravalvular aortic stenosis and identify the integrin β3 pathway as a therapeutic target in this disease.
From the JCB