Highlights d An unbiased LC-MS screen reveals FAMIN as a purine nucleoside enzyme d FAMIN combines adenosine phosphorylase with ADA-, PNP-, and MTAP-like activities d FAMIN enables a purine nucleotide cycle (PNC) preventing cytoplasmic acidification d The FAMIN-dependent PNC balances the glycolysismitochondrial redox interface

Due to a production error, the last name of author Ana Belé n Iglesias-Romero was misspelled as ''Inglesias-Romero.'' This error has been corrected online, and we apologize for any confusion we may have caused.

Ultrasmall gold nanoparticles (2 nm) easily penetrate the membranes of intestinal murine epithelial cells (MODE‐K) and colorectal cancer cells (CT‐26). They are also taken up by 3D spheroids (400 µm) of these cell types and primary gut organoids (500 µm). In contrast, dissolved dyes are not taken up by any of these cells or 3D structures. The distribution of fluorescent ultrasmall gold nanoparticles inside cells, spheroids, and gut organoids is examined by confocal laser scanning microscopy. Nanoparticles conjugated with the cytostatic drug doxorubicin and a fluorescent dye exhibit significantly greater cytotoxicity toward CT‐26 tumor spheroids than equally concentrated dissolved doxorubicin, probably because they enter the interior of a spheroid much more easily than dissolved doxorubicin. Comprehensive analyses show that the cellular uptake of ultrasmall gold nanoparticles occurs by different endocytosis pathways.

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A wide range of microbial pathogens is capable of entering the gastrointestinal tract, causing infectious diarrhea and colitis. A finely tuned balance between different cytokines is necessary to eradicate the microbial threat and to avoid infection complications. The current study identified IL-33 as a critical regulator of the immune response to the enteric pathogen Citrobacter rodentium. We observed that deficiency of the IL-33 signaling pathway attenuates bacterial-induced colitis. Conversely, boosting this pathway strongly aggravates the inflammatory response and makes the mice prone to systemic infection. Mechanistically, IL-33 mediates its detrimental effect by enhancing gut permeability and by limiting the induction of protective T helper 17 cells at the site of infection, thus impairing host defense mechanisms against the enteric pathogen. Importantly, IL-33-treated infected mice supplemented with IL-17A are able to resist the otherwise strong systemic spreading of the pathogen. These findings reveal a novel IL-33/IL-17A crosstalk that controls the pathogenesis of Citrobacter rodentium-driven infectious colitis. Manipulating the dynamics of cytokines may offer new therapeutic strategies to treat specific intestinal infections.