This is the institutional Repository of the Helmholtz Centre for Infection Research in Braunschweig/Germany (HZI), the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarbrücken/Germany, the TWINCORE Zentrum für Exprerimentelle und Klinische Infektionsforschung, Hannover/Germany,Helmholtz-Institut für RNA-basierte Infektionsforschung (HIRI), Würzburg/Germany, Braunschweig Integrated Centre for Systems biology (BRICS), Centre for Structural Systems Biology (CSSB) the Study Centre Hannover, Hannover/Germany and the Centre for Individualised Infection Medicine (CiiM).

 

  • Bacteria as genetically programmable producers of bioactive natural products

    Hug, Joachim J.; Krug, Daniel; Müller, Rolf (2020-04-01)
  • Repositories for Taxonomic Data: Where We Are and What is Missing.

    Miralles, Aurélien; Bruy, Teddy; Wolcott, Katherine; Scherz, Mark D; Begerow, Dominik; Beszteri, Bank; Bonkowski, Michael; Felden, Janine; Gemeinholzer, Birgit; Glaw, Frank; et al. (2020-11-01)
  • A dynamic CD2-rich compartment at the outer edge of the immunological synapse boosts and integrates signals.

    Demetriou, Philippos; Abu-Shah, Enas; Valvo, Salvatore; McCuaig, Sarah; Mayya, Viveka; Kvalvaag, Audun; Starkey, Thomas; Korobchevskaya, Kseniya; Lee, Lennard Y W; Friedrich, Matthias; et al. (2020-09-14)
    The CD2-CD58 recognition system promotes adhesion and signaling and counters exhaustion in human T cells. We found that CD2 localized to the outer edge of the mature immunological synapse, with cellular or artificial APC, in a pattern we refer to as a 'CD2 corolla'. The corolla captured engaged CD28, ICOS, CD226 and SLAM-F1 co-stimulators. The corolla amplified active phosphorylated Src-family kinases (pSFK), LAT and PLC-γ over T cell receptor (TCR) alone. CD2-CD58 interactions in the corolla boosted signaling by 77% as compared with central CD2-CD58 interactions. Engaged PD-1 invaded the CD2 corolla and buffered CD2-mediated amplification of TCR signaling. CD2 numbers and motifs in its cytoplasmic tail controlled corolla formation. CD8+ tumor-infiltrating lymphocytes displayed low expression of CD2 in the majority of people with colorectal, endometrial or ovarian cancer. CD2 downregulation may attenuate antitumor T cell responses, with implications for checkpoint immunotherapies.
  • Cell-substrate adhesion drives Scar/WAVE activation and phosphorylation by a Ste20-family kinase, which controls pseudopod lifetime.

    Singh, Shashi Prakash; Thomason, Peter A; Lilla, Sergio; Schaks, Matthias; Tang, Qing; Goode, Bruce L; Machesky, Laura M; Rottner, Klemens; Insall, Robert H (2020-08-03)
  • Absence of cGAS-mediated type I IFN responses in HIV-1-infected T cells.

    Elsner, Carina; Ponnurangam, Aparna; Kazmierski, Julia; Zillinger, Thomas; Jansen, Jenny; Todt, Daniel; Döhner, Katinka; Xu, Shuting; Ducroux, Aurélie; Kriedemann, Nils; et al. (2020-07-24)
    The DNA sensor cGAS catalyzes the production of the cyclic dinucleotide cGAMP, resulting in type I interferon responses. We addressed the functionality of cGAS-mediated DNA sensing in human and murine T cells. Activated primary CD4+ T cells expressed cGAS and responded to plasmid DNA by upregulation of ISGs and release of bioactive interferon. In mouse T cells, cGAS KO ablated sensing of plasmid DNA, and TREX1 KO enabled cells to sense short immunostimulatory DNA. Expression of IFIT1 and MX2 was downregulated and upregulated in cGAS KO and TREX1 KO T cell lines, respectively, compared to parental cells. Despite their intact cGAS sensing pathway, human CD4+ T cells failed to mount a reverse transcriptase (RT) inhibitor-sensitive immune response following HIV-1 infection. In contrast, infection of human T cells with HSV-1 that is functionally deficient for the cGAS antagonist pUL41 (HSV-1ΔUL41N) resulted in a cGAS-dependent type I interferon response. In accordance with our results in primary CD4+ T cells, plasmid challenge or HSV-1ΔUL41N inoculation of T cell lines provoked an entirely cGAS-dependent type I interferon response, including IRF3 phosphorylation and expression of ISGs. In contrast, no RT-dependent interferon response was detected following transduction of T cell lines with VSV-G-pseudotyped lentiviral or gammaretroviral particles. Together, T cells are capable to raise a cGAS-dependent cell-intrinsic response to both plasmid DNA challenge or inoculation with HSV-1ΔUL41N. However, HIV-1 infection does not appear to trigger cGAS-mediated sensing of viral DNA in T cells, possibly by revealing viral DNA of insufficient quantity, length, and/or accessibility to cGAS.

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