Cutting Edge: The RIG-I Ligand 3pRNA Potently Improves CTL Cross-Priming and Facilitates Antiviral Vaccination

Hochheiser, Katharina; Klein, Marika; Gottschalk, Catherine; Hoß, Florian; Scheu, Stefanie; Coch, Christoph; Hartmann, Gunther; Kurts, Christian

doi:10.4049/jimmunol.1501958

Cited by 43 publications

(42 citation statements)

References 26 publications

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“…We hypothesized that PorB, as a TLR2 agonist might enhance cross-presentation of soluble OVA. T cells, derived from OT-I transgenic mice are a well established model to investigate MHC class I antigen recognition by antigen specific CD8 T cell in in vitro 39 and in vivo 37 . OVA antigen uptake, protelytical degradation and presentation in context of MHC class I will trigger recognition of the “ SIINFEKL ” peptide - MHC class I complex on the APC by OT-I derived CD8 T cells.…”

Section: Resultsmentioning

confidence: 99%

The TLR2 Binding Neisserial Porin PorB Enhances Antigen Presenting Cell Trafficking and Cross-presentation

Reiser

Mosaheb

Lisk

et al. 2017

Sci Rep

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TOLL-like receptor (TLR) ligands activate both innate and adaptive immune cells, while modulating the cellular immune response. The outer membrane protein (OMP) from Neisseria meninigitidis, PorB, is a naturally occurring TLR2 ligand and functions as an adjuvant. Here, we demonstrate that PorB increases the level of OVA in the endo-/lysosomal cellular compartment of BMDCs, increases antigen presenting cell (APC) trafficking to draining lymph nodes, and enhances antigen cross-presentation. PorB is capable of mounting an antigen specific T cell response by efficiently stimulating antigen cross-presentation in vivo and in vitro assessed by BMDC OT-I cocultivation assays. The enhanced antigen cross-presentation and the increased APC recruitment to secondary lymphoid tissues expand the scope of known adjuvant effects of PorB on the immune system. Our findings lead to a better understanding of how TLR-ligand based adjuvants can alter and modulate immune responses.

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Section: Resultsmentioning

confidence: 99%

The TLR2 Binding Neisserial Porin PorB Enhances Antigen Presenting Cell Trafficking and Cross-presentation

Reiser

Mosaheb

Lisk

et al. 2017

Sci Rep

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“…RIG-I agonists have also been successfully used as vaccine adjuvants: M8 and 5’-pppRNA, in combination with influenza hemagglutinin as antigen, protected mice against challenge with a lethal inoculation of influenza, an effect dependent on antibody production and cytotoxic T lymphocyte activation [14, 91]. With their ability to induce tumor cell death and lymphocyte cross-priming, RIG-I ligands are among the most promising molecules for the development of new immune-stimulatory adjuvants in cancer vaccines [69].…”

Section: Implications Of Sting and Rig-i Agonists In Cancer Therapymentioning

confidence: 99%

Crosstalk between Cytoplasmic RIG-I and STING Sensing Pathways

Zevini

Olagnier

Hiscott

2017

Trends in Immunology

275

198

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Detection of evolutionary conserved molecules on microbial pathogens by host immune sensors represents the initial trigger of the immune response against infection. Cytosolic receptors sense viral and intracellular bacterial genomes, as well as nucleic acids produced during replication. Once activated, these sensors trigger multiple signaling cascades, converging on the production of type I interferons and proinflammatory cytokines. Although distinct classes of receptors are responsible for the RNA and DNA sensing, the downstream signaling components are physically and functionally interconnected. This review will highlight the importance of the crosstalk between RIG-I-MAVS RNA sensing and the cGAS-STING DNA sensing pathways in potentiating efficient antiviral responses. The potential of cGAS-STING manipulation as a component of cancer immunotherapy will also be reviewed.

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“…Based on this tumor selective activity and a favorable toxicity profile, RIG-I-specific ligands are currently being developed for immunotherapy of cancer (Duewell et al, , 2015Ellermeier et al, 2013;Schnurr & Duewell, 2013. Part of the potent antitumor activity of RIG-I ligands is its ability to promote crosspresentation of antigens to CD8 T cells and to induce cytotoxic activity (Hochheiser et al, 2016). RIG-I ligands show strong therapeutic activity in viral infection models such as influenza (Weber-Gerlach & Weber, 2016).…”

Section: Rig-imentioning

confidence: 99%

Nucleic Acid Immunity

Hartmann

2017

Advances in Immunology

215

169

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Organisms throughout biology need to maintain the integrity of their genome. From bacteria to vertebrates, life has established sophisticated mechanisms to detect and eliminate foreign genetic material or to restrict its function and replication. Tremendous progress has been made in the understanding of these mechanisms which keep foreign or unwanted nucleic acids from viruses or phages in check. Mechanisms reach from restriction-modification systems and CRISPR/Cas in bacteria and archaea to RNA interference and immune sensing of nucleic acids, altogether integral parts of a system which is now appreciated as nucleic acid immunity. With inherited receptors and acquired sequence information, nucleic acid immunity comprises innate and adaptive components. Effector functions include diverse nuclease systems, intrinsic activities to directly restrict the function of foreign nucleic acids (e.g., PKR, ADAR1, IFIT1), and extrinsic pathways to alert the immune system and to elicit cytotoxic immune responses. These effects act in concert to restrict viral replication and to eliminate virus-infected cells. The principles of nucleic acid immunity are highly relevant for human disease. Besides its essential contribution to antiviral defense and restriction of endogenous retroelements, dysregulation of nucleic acid immunity can also lead to erroneous detection and response to self nucleic acids then causing sterile inflammation and autoimmunity. Even mechanisms of nucleic acid immunity which are not established in vertebrates are relevant for human disease when they are present in pathogens such as bacteria, parasites, or helminths or in pathogen-transmitting organisms such as insects. This review aims to provide an overview of the diverse mechanisms of nucleic acid immunity which mostly have been looked at separately in the past and to integrate them under the framework nucleic acid immunity as a basic principle of life, the understanding of which has great potential to advance medicine.

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Cutting Edge: The RIG-I Ligand 3pRNA Potently Improves CTL Cross-Priming and Facilitates Antiviral Vaccination

Cited by 43 publications

References 26 publications

The TLR2 Binding Neisserial Porin PorB Enhances Antigen Presenting Cell Trafficking and Cross-presentation

The TLR2 Binding Neisserial Porin PorB Enhances Antigen Presenting Cell Trafficking and Cross-presentation

Crosstalk between Cytoplasmic RIG-I and STING Sensing Pathways

Nucleic Acid Immunity

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