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Unc-93 homolog B1 (UNC93B1) is a key regulator of nucleic acid (NA)-sensing Toll-like receptors (TLRs). Loss of NA-sensing TLR responses in UNC93B1-deficient patients facilitates Herpes simplex virus type 1 (HSV-1) encephalitis. UNC93B1 is thought to guide NA-sensing TLRs from the endoplasmic reticulum (ER) to their respective endosomal signaling compartments and to guide the flagellin receptor TLR5...
Long-term epigenetic reprogramming of innate immune cells in response to microbes, also termed “trained immunity,” causes prolonged altered cellular functionality to protect from secondary infections. Here, we investigated whether sterile triggers of inflammation induce trained immunity and thereby influence innate immune responses. Western diet (WD) feeding of Ldlr−/− mice induced systemic inflammation,...
A deep understanding of the immune landscape in human cancer is essential for guiding the development of immunotherapy to benefit more patients with long-lasting efficacy. Now, two studies from Lavin et al. and Chevrier et al. employ mass cytometry to study immune infiltrates in lung adenocarcinoma and clear cell renal cell carcinoma, respectively.
Sensing of nucleic acids (NAs) by Toll-like receptors (TLRs) is crucial in the host defence against viruses and bacteria. Yet, these TLRs can contribute to autoimmunity. UNC93B1 is a key-regulator of NA-sensing TLRs by controlling the translocation of TLRs from the ER into endolysosomes. Without functional UNC93B1, NA-sensing TLRs are retained in the ER, incapable of ligand recognition. Patients lacking...
Endosomal toll-like receptors, namely human TLR3, TLR7, TLR8, and TLR9 sense nucleic acids (NAs) derived from viruses and bacteria. Yet, these TLRs can also contribute to autoimmunity by recognizing host NAs. NA-sensing TLR activity is highly regulated by the correct subcellular localization. Experimental mislocalization of endosomal TLRs to the cell surface leads to insufficient microbial recognition...
Interferon (IFN) regulatory factors (IRFs) are transcription factors with versatile functions in the regulation of innate and adaptive immune responses. In the current issue of the European Journal of Immunology, Steinhagen et al. [Eur. J. Immunol. 2013. 43: 1896–1906] investigate the regulation of IFN‐β and IL‐6 induction in human plasmacytoid DCs stimulated with CpG DNA. Using RNA interference studies,...
The molecular mechanism behind alum adjuvanticity is probably the oldest secret of immunology. In this issue of Immunity, Kuroda et al. (2011) and Kool et al. (2011) identify NLRP3 inflammasome-independent signaling to be crucial for the Th2 cell response induced by aluminum salts.
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