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Jiyoun Min, Dongchan Yang Sung, Mirang Kim, Keeok Haam, Anji Yoo, Jae-Hoon Choi, Barbara U Schraml, Yong Sung Kim, Dongsup Kim, Suk-Jo Kang
The spatiotemporal regulation of immune cells in lymph nodes (LNs) is crucial for mounting protective T-cell responses, which are orchestrated by dendritic cells (DCs). However, it is unclear how the DC subsets are altered by the inflammatory milieu of LNs. Here, we show that the inflamed LNs of Listeria-infected mice are characterized by the clustering of neutrophils and monocytes and IFN-γ production. Significantly, the early inflammatory responses are coupled with the differentiation of not one, but two types of CD64+ CD11c+ MHCII+ inflammatory DCs...
March 16, 2018: Experimental & Molecular Medicine
Matthew A Lakins, Ehsan Ghorani, Hafsa Munir, Carla P Martins, Jacqueline D Shields
Tumours have developed strategies to interfere with most steps required for anti-tumour immune responses. Although many populations contribute to anti-tumour responses, tumour-infiltrating cytotoxic T cells dominate, hence, many suppressive strategies act to inhibit these. Tumour-associated T cells are frequently restricted to stromal zones rather than tumour islands, raising the possibility that the tumour microenvironment, where crosstalk between malignant and "normal" stromal cells exists, may be critical for T cell suppression...
March 5, 2018: Nature Communications
Connie B Gilfillan, Sabine Kuhn, Camille Baey, Evelyn J Hyde, Jianping Yang, Christiane Ruedl, Franca Ronchese
In the steady state, tumors harbor several populations of dendritic cells (DCs) and myeloid cells that are key regulators of the intratumoral immune environment. Among these cells, migratory CD103+ cross-presenting DCs are thought to be critical for tumor-specific CTL responses and tumor resistance. However, it is unclear whether this prominent role also extends to immunotherapy. We used a murine orthotopic mammary tumor model, as well as Clec9A-diphtheria toxin receptor mice that can be depleted of the specialized cross-presenting CD8α+ and CD103+ DC1 subsets, to investigate the role of these DCs in immunotherapy...
March 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Liping Qiu, Michael Valente, Yusuf Dolen, Eliezer Jäger, Martin Ter Beest, Liyan Zheng, Carl G Figdor, Martijn Verdoes
The activation of tumor-specific effector immune cells is key for successful immunotherapy and vaccination is a powerful strategy to induce such adaptive immune responses. However, the generation of effective anticancer vaccines is challenging. To overcome these challenges, a novel straight-forward strategy of adjuvant-induced tumor antigen assembly to generate nanovaccines with superior antigen/adjuvant loading efficiency is developed. To protect nanovaccines in circulation and to introduce additional functionalities, a biocompatible polyphenol coating is installed...
March 1, 2018: Small
J Magarian Blander
Antigen cross-presentation is an adaptation of the cellular process of loading MHC-I molecules with endogenous peptides during their biosynthesis within the endoplasmic reticulum. Cross-presented peptides derive from internalized proteins, microbial pathogens, and transformed or dying cells. The physical separation of internalized cargo from the endoplasmic reticulum, where the machinery for assembling peptide-MHC-I complexes resides, poses a challenge. To solve this problem, deliberate rewiring of organelle communication within cells is necessary to prepare for cross-presentation, and different endocytic receptors and vesicular traffic patterns customize the emergent cross-presentation compartment to the nature of the peptide source...
February 28, 2018: Annual Review of Immunology
Bijun Zeng, Anton Pj Middelberg, Adrian Gemiarto, Kelli MacDonald, Alan G Baxter, Meghna Talekar, Davide Moi, Kirsteen M Tullett, Irina Caminschi, Mireille H Lahoud, Roberta Mazzieri, Riccardo Dolcetti, Ranjeny Thomas
Non-antigen-specific stimulatory cancer immunotherapies are commonly complicated by off-target effects. Antigen-specific immunotherapy, combining viral tumor antigen or personalised neo-epitopes with immune targeting, offers a solution. However, the lack of flexible systems targeting tumor antigens to cross-presenting dendritic cells (DCs) limits clinical development. Although antigen-anti-CLEC-9A mAb conjugates target cross-presenting DCs, adjuvant must be co-delivered for cytotoxic T-cell (CTL) induction...
February 27, 2018: Journal of Clinical Investigation
Yuko Matsuoka, Yoko Kawauchi, Yasuhiro Kuroda, Kiyotaka Kawauchi, Naoya Kojima
Oligomannose-coated liposomes (OMLs), containing entrapped antigens, serve as effective antigen delivery vehicles and as a novel adjuvant to induce antigen-specific cellular immune responses. However, in vitro activation of antigen-presenting cells (APCs) by OMLs has not yet been demonstrated. In this paper, we found that OMLs can deliver the antigens and the stimulatory signals into inflammatory monocytes in vitro, leading to differentiation of the cells to mature APCs. When OMLs were co-cultured with peripheral blood mononuclear cells from C57BL/6 mice in the presence of mouse serum, OMLs were preferentially incorporated into both Ly6Chigh monocytes and Ly6Clow monocytes, which are referred to as murine inflammatory and resident monocytes, respectively...
February 22, 2018: International Immunopharmacology
Shuang Wang, Dezhi Ni, Hua Yue, Nana Luo, Xiaobo Xi, Yugang Wang, Min Shi, Wei Wei, Guanghui Ma
Therapeutic vaccines possess particular advantages and show promising potential to combat burdening diseases, such as acquired immunodeficiency syndrome, hepatitis, and even cancers. An efficient therapeutic vaccine would strengthen the immune system and eventually eliminate target cells through cytotoxic T lymphocytes (CTLs). Unfortunately, insufficient efficacy in triggering such an adaptive immune response is a problem that remains unsolved. To achieve efficient cellular immunity, antigen-presenting cells must capture and further cross-present disease-associated antigens to CD8 T cells via major histocompatibility complex I molecules...
February 22, 2018: Small
Magdalena Ewa Król, Michał Król
The aim of the study was not only to demonstrate whether eye-movement-based task decoding was possible but also to investigate whether eye-movement patterns can be used to identify cognitive processes behind the tasks. We compared eye-movement patterns elicited under different task conditions, with tasks differing systematically with regard to the types of cognitive processes involved in solving them. We used four tasks, differing along two dimensions: spatial (global vs. local) processing (Navon, Cognit Psychol, 9(3):353-383 1977) and semantic (deep vs...
February 20, 2018: Psychological Research
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
No abstract text is available yet for this article.
February 15, 2018: Journal of Experimental Medicine
F Q Cao, M M Yan, Y J Liu, L X Liu, L Lu, H Wang, Ch Zhang, H F Sun, D L Kong, G L Ma
Herein, the photosensitizer indocyanine green (ICG) is used to induce the self-assembly of antigens to form nanovaccines. Under near-infrared (NIR) laser irradiation, reactive oxygen species can be generated by nanovaccines to disrupt the membranes of endo/lysosomes, which helps to release antigens into the cytosol efficiently, thereby enhancing antigen cross-presentation and anti-cancer immunity. To the best of our knowledge, this study represents the first example of ICG as a biocompatible adjuvant to improve cancer vaccine efficacy...
February 13, 2018: Biomaterials Science
Héctor Parra-Sánchez, Lucinda Puebla-Clark, Mónica Reséndiz, Olivia Valenzuela, Jesús Hernández
Conventional dendritic cells (cDCs) are divided into the following different subtypes: cDC1, which promotes a Th1 response, and cDC2, which stimulates a Th2 and Th17 response. These cells have not been characterized in porcine lymphoid tissues. DEC205 is a receptor that increases antigen presentation and allows DCs to cross-present antigens. The objectives of this work were to characterize cDCs subsets in the tonsil, submaxillary and mesenteric lymph nodes and spleen lymphoid tissues and to determine their expression of DEC205 by flow cytometry...
February 9, 2018: Molecular Immunology
Irene Soleto, Uwe Fischer, Carolina Tafalla, Aitor G Granja
Dendritic cells (DCs) are highly specialized antigen-presenting cells that bridge innate and adaptive immune responses in vertebrates, being key modulators in the initiation of specific responses. Although teleost fish present the main elements of a fully developed adaptive immune system, not many studies have focused on identifying specific DC subsets in teleost species. Previous work from our group identified in rainbow trout (Oncorhynchus mykiss) skin a DC subpopulation co-expressing CD8α and major histocompatibility complex II β on the cell surface...
2018: Frontiers in Immunology
Grammatiki Fotaki, Chuan Jin, Mohanraj Ramachandran, Iliana Kyriaki Kerzeli, Alex Karlsson-Parra, Di Yu, Magnus Essand
Accumulating evidence support an important role for endogenous bystander dendritic cells (DCs) in the efficiency of autologous patient-derived DC-vaccines, as bystander DCs take up material from vaccine-DCs, migrate to draining lymph node and initiate antitumor T-cell responses. We examined the possibility of using allogeneic DCs as vaccine-DCs to activate bystander immune cells and promote antigen-specific T-cell responses. We demonstrate that human DCs matured with polyI:C, R848 and IFN-γ (denoted COMBIG) in combination with an infection-enhanced adenovirus vector (denoted Ad5M) exhibit a pro-inflammatory state...
2018: Oncoimmunology
Elien M Doorduijn, Marjolein Sluijter, Koen A Marijt, Bianca J Querido, Sjoerd H van der Burg, Thorbald van Hall
Cancers frequently evade immune-recognition by lowering peptide:MHC-I complexes on their cell surface. Limited peptide supply due to TAP-deficiency results in such MHC-Ilow immune-escape variants. Previously, we reported on a category of TAP-independent self-peptides, called TEIPP, with selective presentation by these tumors. Here we demonstrate that in contrast to T cells specific for conventional tumor antigens, TEIPP-directed T cells remain naïve in mice bearing immune-escaped tumors. This unaffected state was caused by low levels of MHC-I on the tumors and the failure to cross-present low levels of antigenic protein by host APCs...
2018: Oncoimmunology
Jinjin Zhao, Ning Pan, Fang Huang, Mohanad Aldarouish, Zhifa Wen, Rong Gao, Yuye Zhang, Hong-Ming Hu, Yanfei Shen, Li-Xin Wang
A simple and effective strategy was developed to enrich ubiquitinated proteins (UPs) from cancer cell lysate using the α-Al2O3 nanoparticles covalently linked with ubiquitin binding protein (Vx3) (denoted as: α-Al2O3-Vx3) via a chemical linker. The functionalized α-Al2O3-Vx3 showed long-term stability and high efficiency for the enrichment of UPs from cancer cell lysates. Flow cytometry analysis results indicated dendritic cells (DCs) could more effectively phagocytize the covalently linked α-Al2O3-Vx3-UPs than the physical mixture of α-Al2O3 and Vx3-UPs (α-Al2O3/Vx3-UPs)...
January 31, 2018: Bioconjugate Chemistry
Hao Jiang, Qin Wang, Lin Li, Qin Zeng, Hanmei Li, Tao Gong, Zhirong Zhang, Xun Sun
Due to its safety and efficacy, aluminum hydroxide is used as an immune adjuvant in human vaccines for over 80 years. Being a Th2 stimulator, the classical gel-like adjuvant, however, fails to generate CD8+ T cell responses, which are important for cancer vaccines. Here, aluminum hydroxide is turned from gel into nano-sized vaccine carriers AlO(OH)-polymer nanoparticles (APNs) to promote their lymphatic migration. After actively uptaken via scavenger receptor-A by antigen-presenting cells (APCs) resident in lymph nodes (LNs), APNs destabilize lysosomes resulting in efficient cytosolic delivery and cross-presentation of antigens...
January 2018: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Blake F Frey, Jiansheng Jiang, Yongjun Sui, Lisa F Boyd, Bin Yu, Gwen Tatsuno, Rolf Billeskov, Shahram Solaymani-Mohammadi, Phillip W Berman, David H Margulies, Jay A Berzofsky
Unlike cytosolic processing and presentation of viral Ags by virus-infected cells, Ags first expressed in infected nonprofessional APCs, such as CD4+ T cells in the case of HIV, are taken up by dendritic cells and cross-presented. This generally requires entry through the endocytic pathway, where endosomal proteases have first access for processing. Thus, understanding virus escape during cross-presentation requires an understanding of resistance to endosomal proteases, such as cathepsin S (CatS). We have modified HIV-1MN gp120 by mutating a key CatS cleavage site (Thr322Thr323) in the V3 loop of the immunodominant epitope IGPGRAFYTT to IGPGRAFYVV to prevent digestion...
January 26, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Hyejin Kim, Takashi Kimoto, Satoko Sakai, Etsuhisa Takahashi, Hiroshi Kido
We reported previously that intranasal instillation of a synthetic human pulmonary surfactant with a carboxy vinyl polymer as a viscosity improver, named SF-10, shows potent adjuvanticity for humoral immunity in mice and cynomolgus monkeys. SF-10 effectively induces influenza hemagglutinin vaccine (HAv)-specific IgA in nasal and lung washes and IgG in sera with their neutralizing activities. Since CD8+ T cell-mediated protection is an important requirement for adaptive immunity, we investigated in this study the effects of SF-10 with antigen on local and systemic cell-mediated immunity...
2018: PloS One
Jia Guo, Mengjiao Zhou, Xin Liu, Yunzhi Pan, Runjun Yang, Zhihui Zhao, Boxing Sun
Interferon-gamma-inducible protein 30 (IFI30) is an IFN-γ-inducible protein that is involved in MHC class II-restricted antigen processing and MHC class I-restricted cross-presentation pathways of adaptive immunity. The present study aimed to investigate the effects of porcine IFI30 expression on PRRSV proliferation in host cells. MARC-145 cells and pig Sertoli (ST) cells were infected with PRRSV after transfection with porcine IFI30 expression vectors and an empty vector. PRRSV copy numbers were analyzed by absolute real-time quantitative PCR, and the results showed that porcine IFI30 expression could significantly inhibit PRRSV transcription...
January 20, 2018: Gene
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