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456 Aktuelle Fachpublikationen von Proceedings of the National Academy of Sciences

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Human NLRP3 inflammasome senses multiple types of bacterial RNAs [Immunology and Inflammation]

11.11.2014 | Wenwen Sha; Hiroki Mitoma; Shino Hanabuchi; Musheng Bao; Leiyun Weng; Naoshi Sugimoto; Ying Liu; Zhiqiang Zhang; Jin ..., Proceedings of the National Academy of Sciences current issue, 2014

Inflammasomes are multiprotein platforms that activate caspase-1, which leads to the processing and secretion of the proinflammatory cytokines IL-1β and IL-18. Previous studies demonstrated that bacterial RNAs activate the nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin ...

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Role of disease-associated tolerance in infectious superspreaders [Immunology and Inflammation]

04.11.2014 | Smita Gopinath; Joshua S. Lichtman; Donna M. Bouley; Joshua E. Elias; Denise M. Monack, Proceedings of the National Academy of Sciences current issue, 2014

Natural populations show striking heterogeneity in their ability to transmit disease. For example, a minority of infected individuals known as superspreaders carries out the majority of pathogen transmission events. In a mouse model of Salmonella infection, a subset of infected hosts becomes ...

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TLR-dependent phagosome tubulation in dendritic cells promotes phagosome cross-talk to optimize MHC-II antigen presentation [Immunology and Inflammation]

28.10.2014 | Adriana R. Mantegazza; Allison L. Zajac; Alison Twelvetrees; Erika L. F. Holzbaur; Sebastián Amigorena; Michael S. Marks, Proceedings of the National Academy of Sciences current issue, 2014

Dendritic cells (DCs) phagocytose large particles like bacteria at sites of infection and progressively degrade them within maturing phagosomes. Phagosomes in DCs are also signaling platforms for pattern recognition receptors, such as Toll-like receptors (TLRs), and sites for assembly of ...

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Intestinal myofibroblast-specific Tpl2-Cox-2-PGE2 pathway links innate sensing to epithelial homeostasis [Immunology and Inflammation]

28.10.2014 | Manolis Roulis; Christoforos Nikolaou; Elena Kotsaki; Eleanna Kaffe; Niki Karagianni; Vasiliki Koliaraki; Klelia Sal ..., Proceedings of the National Academy of Sciences current issue, 2014

Tumor progression locus-2 (Tpl2) kinase is a major inflammatory mediator in immune cell types recently found to be genetically associated with inflammatory bowel diseases (IBDs). Here we show that Tpl2 may exert a dominant homeostatic rather than inflammatory function in the intestine mediated ...

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Inflammasome activation leads to Caspase-1-dependent mitochondrial damage and block of mitophagy [Immunology and Inflammation]

28.10.2014 | Jiujiu Yu; Hajime Nagasu; Tomohiko Murakami; Hai Hoang; Lori Broderick; Hal M. Hoffman; Tiffany Horng, Proceedings of the National Academy of Sciences current issue, 2014

Inflammasomes are intracellular sensors that couple detection of pathogens and cellular stress to activation of Caspase-1, and consequent IL-1β and IL-18 maturation and pyroptotic cell death. Here, we show that the absent in melanoma 2 (AIM2) and nucleotide-binding oligomerization domain-like ...

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Human TLR10 is an anti-inflammatory pattern-recognition receptor [Immunology and Inflammation]

21.10.2014 | Marije Oosting; Shih-Chin Cheng; Judith M. Bolscher; Rachel Vestering-Stenger; Theo S. Plantinga; Ineke C. Verschuer ..., Proceedings of the National Academy of Sciences current issue, 2014

Toll-like receptor (TLR)10 is the only pattern-recognition receptor without known ligand specificity and biological function. We demonstrate that TLR10 is a modulatory receptor with mainly inhibitory effects. Blocking TLR10 by antagonistic antibodies enhanced proinflammatory cytokine production, ...

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Selection of the lamprey VLRC antigen receptor repertoire [Immunology and Inflammation]

14.10.2014 | Stephen J. Holland; Mingming Gao; Masayuki Hirano; Lakshminarayan M. Iyer; Ming Luo; Michael Schorpp; Max D. Cooper; ..., Proceedings of the National Academy of Sciences current issue, 2014

The alternative adaptive immune system of jawless vertebrates is based on different isotypes of variable lymphocyte receptors (VLRs) that are composed of leucine-rich repeats (LRRs) and expressed by distinct B- and T-like lymphocyte lineages. VLRB is expressed by B-like cells, whereas VLRA and ...

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Tsc1 promotes the differentiation of memory CD8+ T cells via orchestrating the transcriptional and metabolic programs [Immunology and Inflammation]

14.10.2014 | Sharad Shrestha; Kai Yang; Jun Wei; Peer W. F. Karmaus; Geoffrey Neale; Hongbo Chi, Proceedings of the National Academy of Sciences current issue, 2014

Memory CD8+ T cells are an essential component of protective immunity. Signaling via mechanistic target of rapamycin (mTOR) has been implicated in the regulation of the differentiation of effector and memory T cells. However, little is understood about the mechanisms that control mTOR activity, ...

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Disruption of the immune-checkpoint VISTA gene imparts a proinflammatory phenotype with predisposition to the development of autoimmunity [Immunology and Inflammation]

14.10.2014 | Li Wang; Isabelle Le Mercier; Juan Putra; Wenna Chen; Jun Liu; Austin D. Schenk; Elizabeth C. Nowak; Arief A. Suriaw ..., Proceedings of the National Academy of Sciences current issue, 2014

V domain-containing Ig suppressor of T-cell activation (VISTA) is a negative checkpoint regulator that suppresses T cell-mediated immune responses. Previous studies using a VISTA-neutralizing monoclonal antibody show that VISTA blockade enhances T-cell activation. The current study describes a ...

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Antigen affinity and antigen dose exert distinct influences on CD4 T-cell differentiation [Immunology and Inflammation]

14.10.2014 | Simone Keck; Mathias Schmaler; Stefan Ganter; Lena Wyss; Susanne Oberle; Eric S. Huseby; Dietmar Zehn; Carolyn G. King, Proceedings of the National Academy of Sciences current issue, 2014

Cumulative T-cell receptor signal strength and ensuing T-cell responses are affected by both antigen affinity and antigen dose. Here we examined the distinct contributions of these parameters to CD4 T-cell differentiation during infection. We found that high antigen affinity positively correlates ...

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