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Cross-presentation

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https://www.readbyqxmd.com/read/28720467/intradermal-immunization-with-raav1-vector-induces-robust-memory-cd8-t-cell-responses-independently-of-transgene-expression-in-dcs
#1
Alexandre Ghenassia, David-Alexandre Gross, Stéphanie Lorain, Fabiola Tros, Dominique Urbain, Sofia Benkhelifa-Ziyyat, Alain Charbit, Jean Davoust, Pascal Chappert
Recombinant adeno-associated viral (rAAV) vectors exhibit interesting properties as vaccine carriers for their ability to induce long-lasting antibody responses. However, rAAV-based vaccines have been suggested to trigger functionally impaired long-term memory CD8(+) T cell responses, in part due to poor dendritic cell (DC) transduction. Such results, albeit limited to intramuscular immunization, undermined the use of rAAV as vaccine vehicles against intracellular pathogens. We report here that intradermal immunization with a model rAAV2/1-based vaccine drives the development of bona fide long-term memory CD8(+) T cell responses...
July 15, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28716958/%C3%AE-subunit-containing-gabaa-receptor-prevents-overgeneralization-of-fear-in-adult-mice
#2
Wen-Hua Zhang, Jin Zhou, Han-Qing Pan, Xiao-Yang Wang, Wei-Zhu Liu, Jun-Yu Zhang, Xiao-Ping Yin, Bing-Xing Pan
The role of δ subunit-containing GABAA receptor (GABAA(δ)R) in fear generalization is uncertain. Here, by using mice with or without genetic deletion of GABAA(δ)R and using protocols in which the conditioned tone stimuli were cross presented with different nonconditioned stimuli, we observed that when the two tone stimuli were largely similar, both genotypes froze similarly to either of them. However, when they differed markedly, the knockout mice froze much more than their wild-type littermates to the nonconditioned but not conditioned stimuli...
August 2017: Learning & Memory
https://www.readbyqxmd.com/read/28716903/autophagy-related-protein-vps34-controls-the-homeostasis-and-function-of-antigen-cross-presenting-cd8%C3%AE-dendritic-cells
#3
Vrajesh V Parekh, Sudheer K Pabbisetty, Lan Wu, Eric Sebzda, Jennifer Martinez, Jianhua Zhang, Luc Van Kaer
The class III PI3K Vacuolar protein sorting 34 (Vps34) plays a role in both canonical and noncanonical autophagy, key processes that control the presentation of antigens by dendritic cells (DCs) to naive T lymphocytes. We generated DC-specific Vps34-deficient mice to assess the contribution of Vps34 to DC functions. We found that DCs from these animals have a partially activated phenotype, spontaneously produce cytokines, and exhibit enhanced activity of the classic MHC class I and class II antigen-presentation pathways...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28708252/redundant-and-regulatory-roles-for-tlrs-in-leishmania-infection
#4
REVIEW
Prashant Chauhan, Divanshu Shukla, Debprasad Chattopadhyay, Bhaskar Saha
Toll-like receptors (TLRs) are germ-line encoded, non-clonal innate immune receptors, which are often the first receptors to recognize the molecular patterns on pathogens. Therefore, the immune response initiated by TLRs does have far-reaching consequences on the outcome of an infection. As soon as the cell surface TLRs and other receptors recognize a pathogen, the pathogen is phagocytosed. Inclusion of TLRs in the phagosome results in quicker phagosomal maturation and stronger adaptive immune response, as TLRs influence costimulatory molecules expression and determinant selection by MHC class-II and by MHC class-I for cross-presentation...
July 14, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28688697/dose-dependent-enhancement-of-t-lymphocyte-priming-and-ctl-lysis-following-ionizing-radiation-in-an-engineered-model-of-oral-cancer
#5
Megan Morisada, Ellen C Moore, Rachel Hodge, Jay Friedman, Harrison A Cash, James W Hodge, James B Mitchell, Clint T Allen
OBJECTIVES: Determine if direct tumor cell cytotoxicity, antigen release, and susceptibility to T-lymphocyte killing following radiation treatment is dose-dependent. MATERIALS AND METHODS: Mouse oral cancer cells were engineered to express full-length ovalbumin as a model antigen. Tumor antigen release with uptake and cross presentation of antigen by antigen presenting cells with subsequent priming and expansion of antigen-specific T-lymphocytes following radiation was modeled in vitro and in vivo...
August 2017: Oral Oncology
https://www.readbyqxmd.com/read/28688576/vamp8-mediated-nox2-recruitment-to-endosomes-is-necessary-for-antigen-release
#6
Ilse Dingjan, Laurent M Paardekooper, Daniëlle R J Verboogen, Gabriele Fischer von Mollard, Martin Ter Beest, Geert van den Bogaart
Cross-presentation of foreign antigen in major histocompatibility complex (MHC) class I by dendritic cells (DCs) requires activation of the NADPH-oxidase NOX2 complex. We recently showed that NOX2 is recruited to phagosomes by the SNARE protein VAMP8 where NOX2-produced reactive oxygen species (ROS) cause lipid oxidation and membrane disruption, promoting antigen translocation into the cytosol for cross-presentation. In this study, we extend these findings by showing that VAMP8 is also involved in NOX2 trafficking to endosomes...
June 23, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28679634/sec61-blockade-by-mycolactone-inhibits-antigen-cross-presentation-independently-of-endosome-to-cytosol-export
#7
Jeff E Grotzke, Patrycja Kozik, Jean-David Morel, Francis Impens, Natalia Pietrosemoli, Peter Cresswell, Sebastian Amigorena, Caroline Demangel
Although antigen cross-presentation in dendritic cells (DCs) is critical to the initiation of most cytotoxic immune responses, the intracellular mechanisms and traffic pathways involved are still unclear. One of the most critical steps in this process, the export of internalized antigen to the cytosol, has been suggested to be mediated by Sec61. Sec61 is the channel that translocates signal peptide-bearing nascent polypeptides into the endoplasmic reticulum (ER), and it was also proposed to mediate protein retrotranslocation during ER-associated degradation (a process called ERAD)...
July 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28666759/a-short-hairpin-rna-based-adjuvant-targeting-nf-%C3%AE%C2%BAb-repressor-i%C3%AE%C2%BAb%C3%AE-promotes-migration-of-dermal-dendritic-cells-to-draining-lymph-nodes-and-antitumor-ctl-responses-induced-by-dna-vaccination
#8
Felipe Gálvez-Cancino, Jonathan Roco, Nicole Rojas-Colonelli, Camila Flores, Paola Murgas, Sebastián Cruz-Gómez, César Oyarce, Manuel Varas-Godoy, Daniela Sauma, Alvaro Lladser
DNA vaccination is an attractive approach to elicit tumor-specific cytotoxic CD8(+) T lymphocytes (CTL), which can mediate protective immunity against tumors. To initiate CTL responses, antigen-encoding plasmids employed for DNA vaccination need to activate dendritic cells (DC) through the stimulation of DNA-sensing innate immune receptors that converge in the activation of the master transcription factor NF-κB. To this end, NF-κB repressor IκBα needs to be degraded, allowing NF-κB to translocate to the nucleus and transcribe proinflammatory target genes, as well as its repressor IκBα...
June 27, 2017: Vaccine
https://www.readbyqxmd.com/read/28663435/critical-role-for-sec22b-dependent-antigen-cross-presentation-in-antitumor-immunity
#9
Andrés Alloatti, Derek C Rookhuizen, Leonel Joannas, Jean-Marie Carpier, Salvador Iborra, Joao G Magalhaes, Nader Yatim, Patrycja Kozik, David Sancho, Matthew L Albert, Sebastian Amigorena
CD8(+) T cells mediate antigen-specific immune responses that can induce rejection of solid tumors. In this process, dendritic cells (DCs) are thought to take up tumor antigens, which are processed into peptides and loaded onto MHC-I molecules, a process called "cross-presentation." Neither the actual contribution of cross-presentation to antitumor immune responses nor the intracellular pathways involved in vivo are clearly established because of the lack of experimental tools to manipulate this process. To develop such tools, we generated mice bearing a conditional DC-specific mutation in the sec22b gene, a critical regulator of endoplasmic reticulum-phagosome traffic required for cross-presentation...
June 29, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28658614/a-critical-analysis-of-the-role-of-snare-protein-sec22b-in-antigen-cross-presentation
#10
S Julia Wu, Yashar S Niknafs, Stephanie H Kim, Katherine Oravecz-Wilson, Cynthia Zajac, Tomomi Toubai, Yaping Sun, Jayendra Prasad, Daniel Peltier, Hideaki Fujiwara, Israel Hedig, Nathan D Mathewson, Rami Khoriaty, David Ginsburg, Pavan Reddy
Cross-presentation initiates immune responses against tumors and viral infections by presenting extracellular antigen on MHC I to activate CD8(+) T cell-mediated cytotoxicity. In vitro studies in dendritic cells (DCs) established SNARE protein SEC22B as a specific regulator of cross-presentation. However, the in vivo contribution of SEC22B to cross-presentation has not been tested. To address this, we generated DC-specific Sec22b knockout (CD11c-Cre Sec22b(fl/fl)) mice. Contrary to the paradigm, SEC22B-deficient DCs efficiently cross-present both in vivo and in vitro...
June 27, 2017: Cell Reports
https://www.readbyqxmd.com/read/28646891/absence-of-batf3-results-in-reduced-liver-pathology-in-mice-infected-with-schistosoma-japonicum
#11
Lin Chen, Donghui Zhang, Wenyue Zhang, Yuxiao Zhu, Min Hou, Bingya Yang, Zhipeng Xu, Minjun Ji, Guanling Wu
BACKGROUND: The involvement of CD8(+)T cells in schistosomiasis is being increasingly appreciated, but the underlying mechanism is not well defined. RESULTS: In this study, we showed that the absence of Batf3 alleviated liver damage in Batf3 (-/-) mice infected with S. japonicum. We found alleviated liver granulomatous inflammation in Batf3 (-/-) mice with schistosomiasis japonica could not be attributed to the difference in schistosome egg or worm burden. The stronger Tc1 cell responses observed in Batf3 (-/-) mice suggested that the deletion of Batf3 resulted in more activation of CD8(+)T cells unexpectedly during the natural infection of schistosomes...
June 24, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28644974/immature-human-dcs-efficiently-translocate-endocytosed-antigens-into-the-cytosol-for-proteasomal-processing
#12
Renato B Baleeiro, Peter Walden
Cross-presentation of endocytosed antigen is essential for induction of CD8 effector T cell responses and a hallmark of dendritic cells (DCs). The mode of antigen processing in this context is controversial and some models imply translocation of the antigen from the endosomes into the cytosol. To test this hypothesis we made use of the pro-apoptotic properties of cytochrome c when in the cytosol, and confirmed that it indeed triggered apoptosis of human immature DCs but only at high concentrations. Proteasome inhibitors reduced the required concentration of cytochrome c thousand-fold, indicating that protein translocated into the cytosol is rapidly degraded by proteasomes...
June 20, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28638786/polyelectrolyte-enrobed-cancer-cells-in-view-of-personalized-immune-therapy
#13
Lien Lybaert, Keun Ah Ryu, Riet De Rycke, Alfred C Chon, Olivier De Wever, Karim Y Vermaelen, Aaron Esser-Kahn, Bruno G De Geest
Targeting the immune system with a personalized vaccine containing cues derived from the patient's malignancy might be a promising approach in the fight against cancer. It includes neo-antigens as well as nonmutated tumor antigens, preferentially leading to an immune response that is directed to a broader range of epitopes compared to strategies involving a single antigen. Here, this paper reports on an elegant method to encapsulate whole cancer cells into polyelectrolyte particles. Porous and nonaggregated microparticles containing dead cancer cells are obtained by admixing mannitol and live cancer cells with oppositely charged polyelectrolytes, dextran sulfate (anionic polysaccharide), and poly-l-arginine (cationic polypeptide) prior to atomization into a hot air stream...
June 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/28619711/igfbp7-deletion-promotes-hepatocellular-carcinoma
#14
Maaged Akiel, Chunqing Guo, Xia Li, Devaraja Rajasekaran, Rachel G Mendoza, Chadia L Robertson, Nidhi Jariwala, Fang Yuan, Mark A Subler, Jolene Windle, Dawn K Garcia, Zhao Lai, Hung-I Harry Chen, Yidong Chen, Shah Giashuddin, Paul B Fisher, Xiang-Yang Wang, Devanand Sarkar
Activation of IGF signaling is a major oncogenic event in diverse cancers, including hepatocellular carcinoma (HCC). In this setting, the insulin-like growth factor binding protein IGFBP7 inhibits IGF signaling by binding the IGF-1 receptor (IGF-1R), functioning as a candidate tumor suppressor. IGFBP7 abrogates tumors by inhibiting angiogenesis and inducing cancer-specific senescence and apoptosis. Here we report that Igfbp7-deficient mice exhibit constitutively active IGF signaling, presenting with pro-inflammatory and immunosuppressive microenvironments and spontaneous liver and lung tumors occurring with increased incidence in carcinogen-treated subjects...
June 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28615415/cutting-edge-the-aging-immune-system-reveals-the-biological-impact-of-direct-antigen-presentation-on-cd8-t-cell-responses
#15
Jennifer L Uhrlaub, Megan J Smithey, Janko Nikolich-Žugich
The vertebrate immune system uses multiple, sometimes redundant, mechanisms to contain pathogenic microorganisms that are always evolving to evade host defenses. Thus, the cowpox virus (CPXV) uses genes encoding CPXV12 and CPXV203 to prevent direct MHC class I presentation of viral peptides by infected cells. However, CD8 T cells are effectively primed against CPXV by cross-presentation of viral Ags in young mice. Old mice accumulate defects in both CD8 T cell activation and cross-presentation. Using a double-deletion mutant (∆12∆203) of CPXV, we show that direct priming of CD8 T cells in old mice yields superior recall responses, establishing a key contribution of this mechanism to host antipoxvirus responses and enhancing our fundamental understanding of how viral manipulation of direct presentation impacts pathogenesis...
July 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28592428/ebv-infection-empowers-human-b-cells-for-autoimmunity-role-of-autophagy-and-relevance-to-multiple-sclerosis
#16
Elena Morandi, S Anwar Jagessar, Bert A 't Hart, Bruno Gran
The efficacy of B cell depletion therapy in multiple sclerosis indicates their central pathogenic role in disease pathogenesis. The B lymphotropic EBV is a major risk factor in multiple sclerosis, via as yet unclear mechanisms. We reported in a nonhuman primate experimental autoimmune encephalomyelitis model that an EBV-related lymphocryptovirus enables B cells to protect a proteolysis-sensitive immunodominant myelin oligodendrocyte glycoprotein (MOG) epitope (residues 40-48) against destructive processing...
June 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28585770/mining-the-proteome-of-leishmania-donovani-for-the-development-of-novel-mhc-class-i-restricted-epitope-for-the-control-of-visceral-leishmaniasis
#17
Manas R Dikhit, Vijay Mahantesh, Akhilesh Kumar, Ajay Amit, Budheswar Dehury, Yangya Prasad Nathsharma, Md Yousuf Ansari, Vahab Ali, Roshan Kamal Topno, Vnr Das, Krishna Pandey, Ganesh Chandra Sahoo, Sanjiva Bimal, Pradeep Das
Although, the precise host defence mechanism(s) is not completely understood, T cell-mediated immune responses is believed to play a pivotal role in controlling parasite infection. Here we target the stage dependent over expressed gene. Here, the consensus based computational approach was adopted for the screening of potential major histocompatibility complex class I restricted epitopes. Based on the computational analysis and previously published report, a set 19 antigenic proteins derived from Leishmania donovani were screened for further characterization as vaccine candidates...
June 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28566683/combinatorial-delivery-of-dual-and-triple-tlr-agonists-via-polymeric-pathogen-like-particles-synergistically-enhances-innate-and-adaptive-immune-responses
#18
Ranjna Madan-Lala, Pallab Pradhan, Krishnendu Roy
Despite decades of research very few vaccine-adjuvants have received FDA approval. Two fundamental challenges plague clinical translation of vaccine-adjuvants: reducing acute toxicities that result from systemic diffusion of many soluble adjuvants, and delivering multiple adjuvants at the same time to mimic the synergistic immune-stimulation of pathogens, while being safe. In order to address these barriers, we evaluated combinations of four clinically relevant immune-agonists, specifically Toll-like receptor (TLR) ligands, using biodegradable, polymer microparticles...
May 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28559542/march9-mediated-ubiquitination-regulates-mhc-i-export-from-the-tgn
#19
Francesca De Angelis Rigotti, Aude De Gassart, Carina Pforr, Florencia Cano, Prudence N'Guessan, Alexis Combes, Voahirana Camossetto, Paul Lehner, Philippe Pierre, Evelina Gatti
Given the heterogeneous nature of antigens, MHC-I intracellular transport intersects with multiple degradation pathways for efficient peptide loading and presentation to cytotoxic T cells. MHC-I loading with peptides in the endoplasmic reticulum (ER) is a tightly regulated process, while post-ER intracellular transport is considered to occur by default, leading to peptide-bearing MHC-I delivery to the plasma membrane. We show here that MHC-I traffic is submitted to a previously uncharacterized sorting step at the trans Golgi network (TGN), dependent on the ubiquitination of its cytoplasmic tail lysine residues...
May 31, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28552634/itraq-based-quantitative-proteomic-analysis-reveals-bai-hu-tang-enhances-phagocytosis-and-cross-presentation-against-lps-fever-in-rabbit
#20
Shidong Zhang, Dongsheng Wang, Shuwei Dong, Zhiqiang Yang, Zuoting Yan
ETHNOPHARMACOLOGICAL RELEVANCE: Bai-Hu-Tang (BHT), a classical anti-febrile Chinese formula comprising of liquorice, anemarrhena rhizome, gypsum and rice, has been traditionally used to anti-febrile treatment and promote the production of body fluid to relieve thirst. In this paper, we aim to explore anti-febrile mechanism of BHT at protein level through analyzing alteration of differentially expressed proteins (DEPs) both lipopolysaccharide (LPS) fever syndrome and that was treated with BHT in rabbits...
May 24, 2017: Journal of Ethnopharmacology
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