TLR9 signals after translocating from the ER to CpG DNA in the lysosome.
AuthorsLatz E, Schoenemeyer A, Visintin A, Fitzgerald KA, Monks BG, Knetter CF, Lien E, Nilsen NJ, Espevik T, Golenbock DT
JournalNat Immunol
PubMed ID14716310
'Microbial DNA sequences containing unmethylated CpG dinucleotides activate Toll-like receptor 9 (TLR9). We have found that TLR9 is localized to the endoplasmic reticulum (ER) of dendritic cells (DCs) and macrophages. Because there is no precedent for immune receptor signaling in the ER, we investigated how TLR9 is activated. We show ... More
Carbohydrate oxidation acidifies endosomes, regulating antigen processing and TLR9 signaling.
AuthorsLewis CJ, Cobb BA,
JournalJ Immunol
PubMed ID20200279
'Phagocytes kill encapsulated microbes through oxidative cleavage of surface carbohydrates, releasing glycan fragments and microbial contents that serve as ligands for immune receptors, which tailor the immune response against the offending pathogen. The glycan fragments serve as MHC class II (MHC II) ligands and innate receptor agonists, whereas microbial proteins ... More
Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization.
AuthorsHornung V, Bauernfeind F, Halle A, Samstad EO, Kono H, Rock KL, Fitzgerald KA, Latz E,
JournalNat Immunol
PubMed ID18604214
'Inhalation of silica crystals causes inflammation in the alveolar space. Prolonged exposure to silica can lead to the development of silicosis, an irreversible, fibrotic pulmonary disease. The mechanisms by which silica and other crystals activate immune cells are not well understood. Here we demonstrate that silica and aluminum salt crystals ... More
Digestion assays in allergenicity assessment of transgenic proteins.
AuthorsHerman RA, Storer NP, Gao Y,
JournalEnviron Health Perspect
PubMed ID16882518
'The food-allergy risk assessment for transgenic proteins expressed in crops is currently based on a weight-of-evidence approach that holistically considers multiple lines of evidence. This approach recognizes that no single test or property is known to distinguish allergens from nonallergens. The stability of a protein to digestion, as predicted by ... More
Loss-of-function mutations in Rab escort protein 1 (REP-1) affect intracellular transport in fibroblasts and monocytes of choroideremia patients.
'BACKGROUND: Choroideremia (CHM) is a progressive X-linked retinopathy caused by mutations in the CHM gene, which encodes Rab escort protein-1 (REP-1), an escort protein involved in the prenylation of Rabs. Under-prenylation of certain Rabs, as a result of loss of function mutations in REP-1, could affect vesicular trafficking, exocytosis and ... More
Allergic airways disease develops after an increase in allergen capture and processing in the airway mucosa.
Authorsvon Garnier C, Wikstrom ME, Zosky G, Turner DJ, Sly PD, Smith M, Thomas JA, Judd SR, Strickland DH, Holt PG, Stumbles PA,
JournalJ Immunol
PubMed ID17947647
'Airway mucosal dendritic cells (AMDC) and other airway APCs continuously sample inhaled Ags and regulate the nature of any resulting T cell-mediated immune response. Although immunity develops to harmful pathogens, tolerance arises to nonpathogenic Ags in healthy individuals. This homeostasis is thought to be disrupted in allergic respiratory disorders such ... More
Quantitative measurement of protein digestion in simulated gastric fluid.
AuthorsHerman RA, Korjagin VA, Schafer BW,
JournalRegul Toxicol Pharmacol
PubMed ID15748795
The digestibility of novel proteins in simulated gastric fluid is considered to be an indicator of reduced risk of allergenic potential in food, and estimates of digestibility for transgenic proteins expressed in crops are required for making a human-health risk assessment by regulatory authorities. The estimation of first-order rate constants ... More
Positively charged cholesterol-recombinant human gelatins foster the cellular uptake of proteins and murine immune reactions.
AuthorsKadengodlu PA, Hebishima T, Takeshima SN, Ito M, Liu M, Abe H, Aida Y, Aigaki T, Ito Y,
JournalInt J Nanomedicine
PubMed ID23091385
Recombinant human gelatins with defined molecular weights were modified with cholesterol to make them amphiphilic in nature. We investigated the feasibility of these modified human gelatins acting as a carrier of antigenic proteins for inducing cellular immunity. The aim of this study was to synthesize novel and effective compounds for ... More
NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals.
AuthorsDuewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, Abela GS, Franchi L, Nuñez G, Schnurr M, Espevik T, Lien E, Fitzgerald KA, Rock KL, Moore KJ, Wright SD, Hornung V, Latz E,
JournalNature
PubMed ID20428172
The inflammatory nature of atherosclerosis is well established but the agent(s) that incite inflammation in the artery wall remain largely unknown. Germ-free animals are susceptible to atherosclerosis, suggesting that endogenous substances initiate the inflammation. Mature atherosclerotic lesions contain macroscopic deposits of cholesterol crystals in the necrotic core, but their appearance ... More
Extracellular antigen processing and presentation by immature dendritic cells.
In antigen presentation to CD4(+) T cells, proteins are degraded to peptide fragments and loaded onto class II MHC molecules in a process involving the peptide exchange factors H-2M (murine) or HLA-DM (human). In many antigen-presenting cells these processes occur in intracellular endosomal compartments, where peptides are generated and loaded ... More
Enzyme cytochemical techniques for metabolic mapping in living cells, with special reference to proteolysis.
AuthorsBoonacker E, Van Noorden CJ
JournalJ Histochem Cytochem
PubMed ID11724895
Specific enzymes play key roles in many pathophysiological processes and therefore are targets for therapeutic strategies. The activity of most enzymes is largely determined by many factors at the post-translational level. Therefore, it is essential to study the activity of target enzymes in living cells and tissues in a quantitative ... More
Eosinophils promote allergic disease of the lung by regulating CD4(+) Th2 lymphocyte function.
AuthorsMacKenzie JR, Mattes J, Dent LA, Foster PS
JournalJ Immunol
PubMed ID11544300
Eosinophils are primarily thought of as terminal effectors of allergic responses and of parasite elimination. However, limited studies suggest a more discrete immunomodulatory role for this leukocyte during these inflammatory responses. In this investigation, we highlight the potential of eosinophils to act as APCs and thus modulators of allergic responses ... More
Polyethylene glycol-modified GM-CSF expands CD11b(high)CD11c(high) but notCD11b(low)CD11c(high) murine dendritic cells in vivo: a comparative analysis with Flt3 ligand.
AuthorsDaro E, Pulendran B, Brasel K, Teepe M, Pettit D, Lynch DH, Vremec D, Robb L, Shortman K, McKenna HJ, Maliszewski CR, Maraskovsky E
JournalJ Immunol
PubMed ID10861034
Dendritic cells (DC) are potent APCs that can be characterized in the murine spleen as CD11b(high)CD11c(high) or CD11b(low)CD11c(high). Daily injection of mice of Flt3 ligand (FL) into mice transiently expands both subsets of DC in vivo, but the effect of administration of GM-CSF on the expansion of DC in vivo ... More
SMAD3 promotes autophagy dysregulation by triggering lysosome depletion in tubular epithelial cells in diabetic nephropathy.
Authors
JournalAutophagy
PubMed ID33043774
Type II alveolar cell MHCII improves respiratory viral disease outcomes while exhibiting limited antigen presentation.
Authors
JournalNat Commun
PubMed ID34183650
Multilayered Magnetic Nanobeads for the Delivery of Peptides Molecules Triggered by Intracellular Proteases.
Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis.
Authors
JournalCell Stem Cell
PubMed ID34529935
The IAP family member BRUCE regulates autophagosome-lysosome fusion.
Authors
JournalNat Commun
PubMed ID29426817
Antigen-loaded monocyte administration induces potent therapeutic antitumor T cell responses.
Authors
JournalJ Clin Invest
PubMed ID31661470
Tumor-Derived Extracellular Vesicles Breach the Intact Blood-Brain Barrier via Transcytosis.
Authors
JournalACS Nano
PubMed ID31479239
Systemic Blockade of Clever-1 Elicits Lymphocyte Activation Alongside Checkpoint Molecule Downregulation in Patients with Solid Tumors: Results from a Phase I/II Clinical Trial.
Authors
JournalClin Cancer Res
PubMed ID34078651
LRRK2 and Rab10 coordinate macropinocytosis to mediate immunological responses in phagocytes.