المؤلفون: Yanyan Ma, Tangxing Jiang, Xun Zhu, Yizhou Xu, Ke Wan, Tingxuan Zhang, Miaorong Xie

المصدر: Frontiers in Immunology, Vol 15 (2024)

مصطلحات موضوعية: dendritic cell, apoptotic cell, efferocytosis, immune regulation, antigen cross-presentation, Treg differentiation, Immunologic diseases. Allergy, RC581-607

الوصف: Efferocytosis, the process of engulfing and removing apoptotic cells, plays an essential role in preserving tissue health and averting undue inflammation. While macrophages are primarily known for this task, dendritic cells (DCs) also play a significant role. This review delves into the unique contributions of various DC subsets to efferocytosis, highlighting the distinctions in how DCs and macrophages recognize and handle apoptotic cells. It further explores how efferocytosis influences DC maturation, thereby affecting immune tolerance. This underscores the pivotal role of DCs in orchestrating immune responses and sustaining immune equilibrium, providing new insights into their function in immune regulation.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2024.1415573/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/a7326480197346c9904169d2846868e6Test

المؤلفون: Rafaela Holtappels, Julia K. Büttner, Kirsten Freitag, Matthias J. Reddehase, Niels A. Lemmermann

المصدر: Frontiers in Immunology, Vol 15 (2024)

مصطلحات موضوعية: antigen cross-presentation, CD8 T-cell priming, direct antigen presentation, effector-memory T cells (TEM), immune evasion, latent infection, Immunologic diseases. Allergy, RC581-607

الوصف: Cytomegalovirus (CMV) infection is the most critical infectious complication in recipients of hematopoietic cell transplantation (HCT) in the period between a therapeutic hematoablative treatment and the hematopoietic reconstitution of the immune system. Clinical investigation as well as the mouse model of experimental HCT have consistently shown that timely reconstitution of antiviral CD8 T cells is critical for preventing CMV disease in HCT recipients. Reconstitution of cells of the T-cell lineage generates naïve CD8 T cells with random specificities among which CMV-specific cells need to be primed by presentation of viral antigen for antigen-specific clonal expansion and generation of protective antiviral effector CD8 T cells. For CD8 T-cell priming two pathways are discussed: “direct antigen presentation” by infected professional antigen-presenting cells (pAPCs) and “antigen cross-presentation” by uninfected pAPCs that take up antigenic material derived from infected tissue cells. Current view in CMV immunology favors the cross-priming hypothesis with the argument that viral immune evasion proteins, known to interfere with the MHC class-I pathway of direct antigen presentation by infected cells, would inhibit the CD8 T-cell response. While the mode of antigen presentation in the mouse model of CMV infection has been studied in the immunocompetent host under genetic or experimental conditions excluding either pathway of antigen presentation, we are not aware of any study addressing the medically relevant question of how newly generated naïve CD8 T cells become primed in the phase of lympho-hematopoietic reconstitution after HCT. Here we used the well-established mouse model of experimental HCT and infection with murine CMV (mCMV) and pursued the recently described approach of up- or down-modulating direct antigen presentation by using recombinant viruses lacking or overexpressing the central immune evasion protein m152 of mCMV, respectively. Our data reveal that the magnitude of the CD8 T-cell response directly reflects the level of direct antigen presentation.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2024.1355153/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/c6a9e7e2512046fc8ea54b9f03241739Test

المؤلفون: Yunting Zhang, Min Jiang, Guangsheng Du, Xiaofang Zhong, Chunting He, Ming Qin, Yingying Hou, Rong Liu, Xun Sun

المصدر: Acta Pharmaceutica Sinica B, Vol 13, Iss 8, Pp 3518-3534 (2023)

مصطلحات موضوعية: Subunit antigen, Self-assembled nanovaccine, Dendritic cell, Mannose receptor, Zoledronic acid, Antigen cross-presentation, Therapeutics. Pharmacology, RM1-950

الوصف: The rise of nanotechnology has opened new horizons for cancer immunotherapy. However, most nanovaccines fabricated with nanomaterials suffer from carrier-related concerns, including low drug loading capacity, unpredictable metabolism, and potential systemic toxicity, which bring obstacles for their clinical translation. Herein, we developed an antigen self-assembled nanovaccine, which was resulted from a simple acryloyl modification of the antigen to induce self-assembly. Furthermore, a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid (Zol) were integrated or absorbed onto the nanoparticles (denoted as MEAO-Z) to intensify the immune response. The synthesized nanovaccine with a diameter of around 70 nm showed successful lymph node transportation, high dendritic cell internalization, promoted costimulatory molecule expression, and preferable antigen cross-presentation. In virtue of the above superiorities, MEAO-Z induced remarkably higher titers of serum antibody, stronger cytotoxic T lymphocyte immune responses and IFN-γ secretion than free antigen and adjuvants. In vivo, MEAO-Z significantly suppressed EG7-OVA tumor growth and prolonged the survival time of tumor-bearing mice. These results indicated the translation promise of our self-assembled nanovaccine for immune potentiation and cancer immunotherapy.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2211383522001472Test; https://doaj.org/toc/2211-3835Test

الوصول الحر: https://doaj.org/article/aa3e8615132c4663a47cfc59450b5a2dTest

المؤلفون: Yingying Hou, Min Chen, Yuan Bian, Xi Zheng, Rongsheng Tong, Xun Sun

المصدر: Acta Pharmaceutica Sinica B, Vol 13, Iss 8, Pp 3321-3338 (2023)

مصطلحات موضوعية: Subunit vaccine, Vaccine design, Lymph node targeting, Dendritic cell subset targeting, B cell modulation, Antigen cross-presentation, Therapeutics. Pharmacology, RM1-950

الوصف: Designing and manufacturing safe and effective vaccines is a crucial challenge for human health worldwide. Research on adjuvant-based subunit vaccines is increasingly being explored to meet clinical needs. Nevertheless, the adaptive immune responses of subunit vaccines are still unfavorable, which may partially be attributed to the immune cascade obstacles and unsatisfactory vaccine design. An extended understanding of the crosstalk between vaccine delivery strategies and immunological mechanisms could provide scientific insight to optimize antigen delivery and improve vaccination efficacy. In this review, we summarized the advanced subunit vaccine delivery technologies from the perspective of vaccine cascade obstacles after administration. The engineered subunit vaccines with lymph node and specific cell targeting ability, antigen cross-presentation, T cell activation properties, and tailorable antigen release patterns may achieve effective immune protection with high precision, efficiency, and stability. We hope this review can provide rational design principles and inspire the exploitation of future subunit vaccines.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2211383523000060Test; https://doaj.org/toc/2211-3835Test

الوصول الحر: https://doaj.org/article/a9c1063d7b924300b936c6f233bdd899Test

المؤلفون: Julia K. Büttner, Sara Becker, Annette Fink, Melanie M. Brinkmann, Rafaela Holtappels, Matthias J. Reddehase, Niels A. Lemmermann

المصدر: Frontiers in Immunology, Vol 14 (2023)

مصطلحات موضوعية: CD8 T cell response, m152/gp40, antigen presentation, antigen cross-presentation, antigen presenting cell (APC), murine cytomegalovirus (mCMV), Immunologic diseases. Allergy, RC581-607

الوصف: CD8 T cells are important antiviral effectors in the adaptive immune response to cytomegaloviruses (CMV). Naïve CD8 T cells can be primed by professional antigen-presenting cells (pAPCs) alternatively by “direct antigen presentation” or “antigen cross-presentation”. In the case of direct antigen presentation, viral proteins are expressed in infected pAPCs and enter the classical MHC class-I (MHC-I) pathway of antigen processing and presentation of antigenic peptides. In the alternative pathway of antigen cross-presentation, viral antigenic material derived from infected cells of principally any cell type is taken up by uninfected pAPCs and eventually also fed into the MHC class-I pathway. A fundamental difference, which can be used to distinguish between these two mechanisms, is the fact that viral immune evasion proteins that interfere with the cell surface trafficking of peptide-loaded MHC-I (pMHC-I) complexes are absent in cross-presenting uninfected pAPCs. Murine cytomegalovirus (mCMV) models designed to disrupt either of the two presentation pathways revealed that both are possible in principle and can substitute each other. Overall, however, the majority of evidence has led to current opinion favoring cross-presentation as the canonical pathway. To study priming in the normal host genetically competent in both antigen presentation pathways, we took the novel approach of enhancing or inhibiting direct antigen presentation by using recombinant viruses lacking or overexpressing a key mCMV immune evasion protein. Against any prediction, the strongest CD8 T-cell response was elicited under the condition of intermediate direct antigen presentation, as it exists for wild-type virus, whereas the extremes of enhanced or inhibited direct antigen presentation resulted in an identical and weaker response. Our findings are explained by direct antigen presentation combined with a negative feedback regulation exerted by the newly primed antiviral effector CD8 T cells. This insight sheds a completely new light on the acquisition of viral immune evasion genes during virus-host co-evolution.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1272166/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/79934bb9fe914af98a35679105d46474Test

المؤلفون: Yicheng Ye, Hao Tian, Jiamiao Jiang, Weichang Huang, Ruotian Zhang, Huaan Li, Lu Liu, Junbin Gao, Haixin Tan, Meihuan Liu, Fei Peng, Yingfeng Tu

المصدر: Advanced Science, Vol 10, Iss 25, Pp n/a-n/a (2023)

مصطلحات موضوعية: antigen cross‐presentation, biodegradable robots, immunotherapy, magnetic actuation, melanoma, Science

الوصف: Abstract An efficient and cost‐effective therapeutic vaccine is highly desirable for the prevention and treatment of cancer, which helps to strengthen the immune system and activate the T cell immune response. However, initiating such an adaptive immune response efficiently remains challenging, especially the deficient antigen presentation by dendritic cells (DCs) in the immunosuppressive tumor microenvironment. Herein, an efficient and dynamic antigen delivery system based on the magnetically actuated OVA‐CaCO3‐SPIO robots (OCS‐robots) is rationally designed for active immunotherapy. Taking advantage of the unique dynamic features, the developed OCS‐robots achieve controllable motion capability under the rotating magnetic field. Specifically, with the active motion, the acid‐responsiveness of OCS‐robots is beneficial for the tumor acidity attenuating and lysosome escape as well as the subsequent antigen cross‐presentation of DCs. Furthermore, the dynamic OCS‐robots boost the crosstalk between the DCs and antigens, which displays prominent tumor immunotherapy effect on melanoma through cytotoxic T lymphocytes (CTLs). Such a strategy of dynamic vaccine delivery system enables the active activation of immune system based on the magnetically actuated OCS‐robots, which presents a plausible paradigm for incredibly efficient cancer immunotherapy by designing multifunctional and novel robot platforms in the future.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2198-3844Test

الوصول الحر: https://doaj.org/article/6337f16c48f249468893b18b187aa726Test

المؤلفون: Laura Padula, Eva Fisher, Natasa Strbo

المصدر: Cells, Vol 13, Iss 1, p 72 (2023)

مصطلحات موضوعية: heat shock proteins, gp96, vaccine, antigen cross presentation, mucosal immunity, innate and adaptive immune responses, Cytology, QH573-671

الوصف: It has been 50 years since Peter Charles Doherty and Rolf M Zinkernagel proposed the principle of “simultaneous dual recognition”, according to which adaptive immune cells recognized “self” and “non-self” simultaneously to establish immunological efficacy. These two scientists shared the 1996 Nobel Prize in Physiology or Medicine for this discovery. Their basic immunological principle became the foundation for the development of numerous vaccine approaches against infectious diseases and tumors, including promising strategies grounded on the use of recombinant gp96-Ig developed by our lab over the last two decades. In this review, we will highlight three major principles of the gp96-Ig vaccine strategy: (1) presentation of pathogenic antigens to T cells (specificity); (2) activation of innate immune responses (adjuvanticity); (3) priming of T cells to home to the epithelial compartments (mucosal immunity). In summary, we provide a paradigm for a vaccine approach that can be rapidly engineered and customized for any future pathogens that require induction of effective tissue-resident memory responses in epithelial tissues.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2073-4409/13/1/72Test; https://doaj.org/toc/2073-4409Test

الوصول الحر: https://doaj.org/article/2fd635b980d34be0b7b132a8267a0dcdTest

المؤلفون: Lucía Biscari, Ma Carmen Maza, Cecilia Farré, Cintia Daniela Kaufman, Sebastian Amigorena, Manuel Fresno, Núria Gironès, Andrés Alloatti

المصدر: Frontiers in Cell and Developmental Biology, Vol 11 (2023)

مصطلحات موضوعية: Sec22b SNARE protein, antigen cross-presentation, Trypanosoma cruzi, dendritic cells, CD8 + T cells, cre-loxp transgenic mice, Biology (General), QH301-705.5

الوصف: Antigen cross-presentation is a vital mechanism of dendritic cells and other antigen presenting cells to orchestrate the priming of cytotoxic responses towards killing of infected or cancer cells. In this process, exogenous antigens are internalized by dendritic cells, processed, loaded onto MHC class I molecules and presented to CD8+ T cells to activate them. Sec22b is an ER-Golgi Intermediate Compartment resident SNARE protein that, in partnership with sintaxin4, coordinates the recruitment of the transporter associated with antigen processing protein and the peptide loading complex to phagosomes, where antigenic peptides that have been proteolyzed in the cytosol are loaded in MHC class I molecules and transported to the cell membrane. The silencing of Sec22b in dendritic cells primary cultures and conditionally in dendritic cells of C57BL/6 mice, critically impairs antigen cross-presentation, but neither affects other antigen presentation routes nor cytokine production and secretion. Mice with Sec22b conditionally silenced in dendritic cells (Sec22b−/−) show deficient priming of CD8+ T lymphocytes, fail to control tumor growth, and are resistant to anti-checkpoint immunotherapy. In this work, we show that Sec22b−/− mice elicit a deficient specific CD8+ T cell response when challenged with sublethal doses of Trypanosoma cruzi trypomastigotes that is associated with increased blood parasitemia and diminished survival.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fcell.2023.1138571/fullTest; https://doaj.org/toc/2296-634XTest

الوصول الحر: https://doaj.org/article/60e4238fe43948da8ba96cb746ee014eTest

المؤلفون: Biscari, Lucía, Maza, Ma Carmen, Farré, Cecilia, Kaufman, Cintia Daniela, Amigorena, Sebastian, Fresno Escudero, Manuel, Gironès, Núria, Alloatti, Andrés

المساهمون: UAM. Departamento de Biología Molecular

مصطلحات موضوعية: Sec22b SNARE protein, antigen cross-presentation, Trypanosoma cruzi, dendritic cells, CD8 + T cells, cre-loxp transgenic mice, Biología y Biomedicina / Biología

الوصف: Antigen cross-presentation is a vital mechanism of dendritic cells and other antigen presenting cells to orchestrate the priming of cytotoxic responses towards killing of infected or cancer cells. In this process, exogenous antigens are internalized by dendritic cells, processed, loaded onto MHC class I molecules and presented to CD8+ T cells to activate them. Sec22b is an ER-Golgi Intermediate Compartment resident SNARE protein that, in partnership with sintaxin4, coordinates the recruitment of the transporter associated with antigen processing protein and the peptide loading complex to phagosomes, where antigenic peptides that have been proteolyzed in the cytosol are loaded in MHC class I molecules and transported to the cell membrane. The silencing of Sec22b in dendritic cells primary cultures and conditionally in dendritic cells of C57BL/6 mice, critically impairs antigen cross-presentation, but neither affects other antigen presentation routes nor cytokine production and secretion. Mice with Sec22b conditionally silenced in dendritic cells (Sec22b−/− ) show deficient priming of CD8+ T lymphocytes, fail to control tumor growth, and are resistant to anti-checkpoint immunotherapy. In this work, we show that Sec22b−/− mice elicit a deficient specific CD8+ T cell response when challenged with sublethal doses of Trypanosoma cruzi trypomastigotes that is associated with increased blood parasitemia and diminished survival ; This research was funded by grants from “Ministerio de Ciencia e Innovación” (SAF 2016–75988-R. PID-2019-104760RB-100), “Comunidad de Madrid (S2017/BMD-3671. INFLAMUNE-CM) to MF “Ministerio de Ciencia, Innovación y Universidades Agencia Estatal de Investigación and Fondo Europeo de Desarrollo Regional (PGC 2018–096132-B-I00 and PID 2021–123389OB-I00 (MICINN/FEDER) to NG CBMSO institutional grants from “Fundación Ramón Areces” and “Banco de Santander” are also acknowledged. AA was suported by the Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación of ...

وصف الملف: application/pdf

العلاقة: Frontiers in Cell and Developmental Biology; Gobierno de España. SAF 2016–75988-R; Gobierno de España. PID-2019-104760RB-100; Gobierno de España. 2018–096132-B-I00; Gobierno de España. 2021–123389OB-I00; Comunidad de Madrid. S-2017/BMD-3671/INFLAMUNE-CM; Frontiers in Cell and Developmental Biology11 (2023): 1138571; 2296-634X (electronic); http://hdl.handle.net/10486/707893Test; 1138571-1; 1138571-9; 11

الإتاحة: https://doi.org/10.3389/fcell.2023.1138571Test
http://hdl.handle.net/10486/707893Test

المؤلفون: Raquel S Laureano, Jenny Sprooten, Isaure Vanmeerbeerk, Daniel M Borras, Jannes Govaerts, Stefan Naulaerts, Zwi N Berneman, Benoit Beuselinck, Kalijn F Bol, Jannie Borst, an Coosemans, Angeliki Datsi, Jitka Fučíková, Lisa Kinget, Bart Neyns, Gerty Schreibelt, Evelien Smits, Rüdiger V Sorg, Radek Spisek, Kris Thielemans, Sandra Tuyaerts, Steven De Vleeschouwer, I Jolanda M de Vries, Yanling Xiao, Abhishek D Garg

المصدر: OncoImmunology, Vol 11, Iss 1 (2022)

مصطلحات موضوعية: Dendritic cells, DAMPs, TAAs, antigen cross-presentation, T cell priming, immune checkpoint blockers, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Dendritic cell (DC)-based vaccination for cancer treatment has seen considerable development over recent decades. However, this field is currently in a state of flux toward niche-applications, owing to recent paradigm-shifts in immuno-oncology mobilized by T cell-targeting immunotherapies. DC vaccines are typically generated using autologous (patient-derived) DCs exposed to tumor-associated or -specific antigens (TAAs or TSAs), in the presence of immunostimulatory molecules to induce DC maturation, followed by reinfusion into patients. Accordingly, DC vaccines can induce TAA/TSA-specific CD8+/CD4+ T cell responses. Yet, DC vaccination still shows suboptimal anti-tumor efficacy in the clinic. Extensive efforts are ongoing to improve the immunogenicity and efficacy of DC vaccines, often by employing combinatorial chemo-immunotherapy regimens. In this Trial Watch, we summarize the recent preclinical and clinical developments in this field and discuss the ongoing trends and future perspectives of DC-based immunotherapy for oncological indications.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2162-402XTest

الوصول الحر: https://doaj.org/article/be78d83094d145fe958410723c8c8404Test