Article
Immunology
Johnathan Canton, Hanna Blees, Conor M. Henry, Michael D. Buck, Oliver Schulz, Neil C. Rogers, Eleanor Childs, Santiago Zelenay, Hefin Rhys, Marie-Charlotte Domart, Lucy Collinson, Andres Alloatti, Cara J. Ellison, Sebastian Amigorena, Venizelos Papayannopoulos, David C. Thomas, Felix Randow, Caetano Reis e Sousa
Summary: DNGR-1 is a dedicated cross-presentation receptor that promotes phagosomal rupture, allowing corpse-associated antigens to access the major histocompatibility complex class I antigen processing pathway. This mechanism reveals the existence of innate immune receptors that couple ligand binding and endocytic vesicle damage to regulate adaptive immunity.
Review
Immunology
Conor M. Henry, Carlos A. Castellanos, Caetano Reis E. Sousa
Summary: In this review, the role of dendritic cell natural killer group receptor-1 (DNGR-1) in cDC1 and its functions in anti-viral and anti-tumor immunity are discussed. The study found that DNGR-1 can promote inducible rupture of phagocytic or endocytic compartments containing dead cell debris, making dead cell-associated antigens accessible to cDC1. Additionally, DNGR-1 can recognize dead cells and participate in immune response. Therefore, the study of DNGR-1 has opened new perspectives into cross-presentation, which may have applications in immunotherapy of cancer and vaccination against viral diseases.
SEMINARS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Takumi Kawasaki, Moe Ikegawa, Kosuke Yunoki, Hifumi Otani, Daisuke Ori, Ken J. Ishii, Etsushi Kuroda, Shiki Takamura, Masahiro Kitabatake, Toshihiro Ito, Ayako Isotani, Taro Kawai
Summary: Alveolar macrophages function as antigen-presenting cells to support the expansion of lung CD8+ memory T cells and play a protective role during viral infection. This process relies on antigen cross-presentation and high expression of interleukin-18 by alveolar macrophages.
Article
Microbiology
Midori Nakamura-Hoshi, Takushi Nomura, Masako Nishizawa, Trang Thi Thu Hau, Hiroyuki Yamamoto, Midori Okazaki, Hiroshi Ishii, Kenzo Yonemitsu, Yuriko Suzaki, Yasushi Ami, Tetsuro Matano
Summary: Human T-cell leukemia virus type 1 (HTLV-1) can proliferate from latently infected cells in the absence of CD8(+) cells, suggesting that CD8(+) cells are responsible for the control of HTLV-1 replication.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biology
Risa Ebina-Shibuya, Erin E. West, Rosanne Spolski, Peng Li, Jangsuk Oh, Majid Kazemian, Daniel Gromer, Phillip Swanson, Ning Du, Dorian B. McGavern, Warren J. Leonard
Summary: TSLP plays a crucial role in the development of diseases such as asthma, atopic dermatitis, and allergic inflammation, but its role in CD8(+) T-cell primary responses and memory CD8(+) T cell responses to secondary viral infection is still controversial. Research has shown that TSLP limits the primary CD8(+) T-cell response to influenza, but has little effect on T cell function and the number of memory CD8(+) T cells generated after influenza infection, while inhibiting memory CD8(+) T-cell responses to secondary viral infections.
Article
Immunology
Stephane Isnard, Etienne X. Hatton, Marco Iannetta, Jean-Baptiste Guillerme, Anne Hosmalin
Summary: IFN-gamma secretion by Ag-specific T cells is tightly regulated by engagement of the TCR. Plasmacytoid dendritic cells (pDC) and conventional DC play a crucial role in the activation of HIV-specific T cells. Noncognate activation mechanism involving production of IFN-alpha, IFN-beta, and TNF-alpha induces intracellular production of IFN-gamma.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Ardiana Moustaki, Jeremy Chase Crawford, Shanta Alli, Yiping Fan, Shannon Boi, Anthony E. Zamora, Natalie M. N. McDonald, Gang Wu, Joy Nakitandwe, Scott Newman, Scott Foy, Antonina Silkov, Paul G. Thomas, Alberto Pappo, Michael A. Dyer, Elizabeth Stewart, Sara Federico, Ben Youngblood
Summary: Age bias affects antitumor immunity, with a young tissue microenvironment leading to an immune response skewed towards a terminal effector state, limiting the window for immunotherapeutic interventions.
SCIENCE IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Judith Grau-Exposito, Nerea Sanchez-Gaona, Nuria Massana, Marina Suppi, Antonio Astorga-Gamaza, David Perea, Joel Rosado, Anna Falco, Cristina Kirkegaard, Ariadna Torrella, Bibiana Planas, Jordi Navarro, Paula Suanzes, Daniel Alvarez-Sierra, Alfonso Ayora, Irene Sansano, Juliana Esperalba, Cristina Andres, Andres Anton, Santiago Ramon y Cajal, Benito Almirante, Ricardo Pujol-Borrell, Vicenc Falco, Joaquin Burgos, Maria J. Buzon, Meritxell Genesca
Summary: The study suggests that lung resident memory T cells play a crucial role in limiting the spread of SARS-CoV-2 and COVID-19. Different clinical outcomes are associated with distinct virus-specific T cell responses, and the persistence of antiviral lung T-RM cells in convalescent patients may help limit reinfection.
NATURE COMMUNICATIONS
(2021)
Article
Biology
You-Yuan Wang, Cheng Zhen, Wei Hu, Hui-Huang Huang, Yan-Jun Li, Ming-Ju Zhou, Jing Li, Yu-Long Fu, Peng Zhang, Xiao-Yu Li, Tao Yang, Jin-Wen Song, Xing Fan, Jun Zou, Si-Run Meng, Ya-Qin Qin, Yan-Mei Jiao, Ruonan Xu, Ji-Yuan Zhang, Chun-Bao Zhou, Jin-Hong Yuan, Lei Huang, Ming Shi, Liang Cheng, Fu-Sheng Wang, Chao Zhang
Summary: Plasma glutamate levels are increased in PLWH and negatively correlate with the anti-HIV function of CD8+ T cells. Metabolic modeling shows that glutamate metabolism is robust in TVM cells. Glutamate inhibits TVM cell function via the mTORC1 pathway. There is an association between metabolic plasticity and CD8+ T cell-mediated HIV control.
COMMUNICATIONS BIOLOGY
(2023)
Article
Allergy
Komal Agrawal, Li Ching Ong, Susan Monkley, Kristofer Thorn, Elisabeth Israelsson, Engin Baturcam, Cassie Rist, Karin Schon, Sophia Blake, Bjorn Magnusson, James Cartwright, Suman Mitra, Abilash Ravi, Nazanin Zounemat-Kermani, Jayendra Kumar Krishnaswamy, Nils Y. Lycke, Ulf Gehrmann, Johan Mattsson
Summary: Patients with asthma experience reduced ability to clear respiratory viral infections due to changes in gene expression in nasal and lung epithelial cells. These changes interfere with the development of lung resident memory T cells, which may contribute to the increased susceptibility of patients with asthma to viral exacerbations.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Microbiology
Alex S. Hartlage, Piyush Dravid, Christopher M. Walker, Amit Kapoor
Summary: The study found that the efficacy of an RHV T cell vaccine is reduced when challenge virus contains escape mutations within MHC class I-restricted epitopes. CD4 T cell help is a critical correlate of vaccine success against heterologous virus challenge. These results have important implications for human vaccination programs against heterogeneous HCV strains.
Review
Immunology
Satomi Ando, Koichi Araki
Summary: Persistent antigenic stimulation leads to T-cell exhaustion, characterized by loss of effector function or physical deletion of specific CD8 T cells. PD-1 expression plays a major role in T-cell dysfunction, and PD-1 blockade has been shown effective against different types of cancer. Understanding the heterogeneity of T-cell exhaustion and mechanisms of PD-1-targeted immunotherapy is crucial to enhance its efficacy.
INTERNATIONAL IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Haochen Yao, Na Shen, Guofeng Ji, Juanjuan Huang, Jiali Sun, Guoqing Wang, Zhaohui Tang, Xuesi Chen
Summary: The study demonstrates the strong antitumor immune response of cisplatin-based nanoparticles in a tumor-bearing mouse model. The sustained retention of nanoparticles leads to persistent tumor MHC-I overexpression, promoting the formation of pMHC-I and enhancing the interaction with T cell receptors. Additionally, the nanoparticles upregulate OX40 on intratumoral CD8+ T cells and synergize with an agonistic OX40 antibody to suppress tumor growth by 89.2%.
Article
Immunology
Martina Damo, D. Scott Wilson, Elyse A. Watkins, Jeffrey A. Hubbell
Summary: Hepatocytes play a crucial role in inducing immunologic tolerance in the liver through cross-presentation of extracellular antigens. This study demonstrates that hepatocytes are capable of efficiently inducing cross-tolerance of specific T cells, providing evidence for their potential as valuable candidates for targeted tolerogenic treatments in vivo.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Andreas Walker, Tatjana Schwarz, Janine Brinkmann-Paulukat, Karin Wisskirchen, Christopher Menne, Elahe Salimi Alizei, Helenie Kefalakes, Martin Theissen, Daniel Hoffmann, Julian Schulze zur Wiesch, Mala K. K. Maini, Markus Cornberg, Anke R. M. Kraft, Verena Keitel, Hans H. H. Bock, Peter A. A. Horn, Robert Thimme, Heiner Wedemeyer, Falko M. M. Heinemann, Tom Luedde, Christoph Neumann-Haefelin, Ulrike Protzer, Joerg Timm
Summary: This study performed a high-resolution analysis of the core(18-27) specific CD8+ T cell and the selected escape pathways in patients with chronic HBV infection. The results demonstrate the promiscuous presentation of the core(18-27) epitope and the selection pressure on the epitope in the context of different HLA class I molecules. Some epitope variants showed evidence for impaired antigen processing and reduced presentation. These findings suggest the importance of considering epitope variants in T cell-based therapy strategies for chronic HBV infection.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Spyridon Makris, Cecilia Johansson
Summary: Innate immune responses are crucial for protecting the neonatal lung, and neonatal lungs respond differently to various innate immune stimuli compared to adult lungs. Specifically, they show a weaker response to respiratory syncytial virus (RSV) but a stronger response to R848 and influenza virus, possibly due to higher levels of cAMP and enhanced responsiveness to extracellular adenosine. These findings have implications for the development of vaccine adjuvants for neonates.
MUCOSAL IMMUNOLOGY
(2021)
Editorial Material
Biochemistry & Molecular Biology
James A. Harker, Cecilia Johansson
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2021)
Review
Immunology
Cecilia Johansson, Freja C. M. Kirsebom
Summary: Viral respiratory infections can cause severe diseases, especially in vulnerable populations like infants and the elderly. Neutrophils are important immune cells that play a role in host defense, but their exact role in viral infections, which replicate intracellularly, is still unclear. Tight regulation of neutrophils is necessary in the lungs to prevent damage to host tissues.
MUCOSAL IMMUNOLOGY
(2021)
Article
Cell Biology
Charlotte M. de Winde, Spyridon Makris, Lindsey J. Millward, Jesus A. Cantoral-Rebordinos, Agnesska C. Benjamin, Victor G. Martinez, Sophie E. Acton
Summary: In adaptive immunity, CLEC-2(+) dendritic cells inhibit podoplanin-dependent actomyosin contractility in fibroblastic reticular cells (FRCs) to allow FRC spreading and lymph node expansion. Podoplanin and its partner proteins CD44 and CD9 are differentially expressed by specific lymph node stromal populations in vivo, and their expression in FRCs is coregulated by CLEC-2. Both CD44 and CD9 suppress podoplanin-dependent contractility and play crucial roles in FRC polarity, alignment, and interactions.
JOURNAL OF CELL SCIENCE
(2021)
Article
Multidisciplinary Sciences
Agata Antepowicz, Omar Habib, Freja Kirsebom, Cecilia Johansson, Deborah R. Gill, Stephen C. Hyde
Summary: In this study, gene delivery approaches using recombinant adeno-associated virus and simian immunodeficiency virus vectors were utilized to achieve sustained in vivo production of Palivizumab in a murine model. Pre-treatment with Palivizumab-expressing vectors provided complete protection against RSV-induced weight loss. This approach offers prophylaxis against RSV infection, potentially reducing treatment costs in vulnerable populations.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Charlotte M. de Winde, Samantha L. George, Eva Crosas-Molist, Yukti Hari-Gupta, Abbey B. Arp, Agnesska C. Benjamin, Lindsey J. Millward, Spyridon Makris, Alexander Carver, Valerio Imperatore, Victor G. Martinez, Victoria Sanz-Moreno, Sophie E. Acton
Summary: Melanoma, an aggressive skin cancer, utilizes amoeboid migration for invasion. The glycoprotein podoplanin has been identified as a potential biomarker in melanoma, enhancing invasion capabilities in the tumor cells.
Review
Cell Biology
Spyridon Makris, Charlotte M. de Winde, Harry L. Horsnell, Jesus A. Cantoral-Rebordinos, Rachel E. Finlay, Sophie E. Acton
Summary: Lymphoid tissue returns to a steady state after each immune response, but its structure and function are influenced by changes in the microenvironment. Imbalance in homeostasis can lead to tissue dysfunction and abnormal immune responses. This Review discusses the role and remodeling of lymphoid tissue in adaptive immunity and disease, including the effects of infection, chronic inflammation, and cancer.
DISEASE MODELS & MECHANISMS
(2022)
Article
Multidisciplinary Sciences
Joschka Hey, Michelle Paulsen, Reka Toth, Dieter Weichenhan, Simone Butz, Jolanthe Schatterny, Reinhard Liebers, Pavlo Lutsik, Christoph Plass, Marcus A. Mall
Summary: Muco-obstructive lung diseases are characterized by epigenetic alterations of airway macrophages, leading to changes in inflammatory responses and impaired phagocytosis and efferocytosis. Targeting these altered macrophages may provide therapeutic approaches to improve the condition of patients with muco-obstructive lung diseases.
NATURE COMMUNICATIONS
(2021)
Article
Microbiology
Augusto Varese, Joy Nakawesi, Ana Farias, Freja C. M. Kirsebom, Michelle Paulsen, Rinat Nuriev, Cecilia Johansson
Summary: Respiratory syncytial virus (RSV) infection presents challenges in eliciting protective memory immune responses. This study uses mouse models to investigate the impact of innate immune response determinants on T-RM cell generation and expansion during RSV infection. The results show that impairment of innate immune recognition and induction of type I interferons lead to reduced expansion and functionality of T-RM cells. Interestingly, treatment with interferon-alpha can restore T-RM cell expansion but not functionality. These findings provide insights into the role of innate immunity in regulating T-RM cell responses to RSV infection.
Article
Immunology
Patricia P. Ogger, Minerva Garcia Martin, Christina Michalaki, Jie Zhou, Jonathan C. Brown, Yue Du, Kamran M. Miah, Omar Habib, Stephen C. Hyde, Deborah R. Gill, Wendy S. Barclay, Cecilia Johansson
Summary: Studies have shown that the type I interferon signaling pathway plays a crucial role in combating SARS-CoV-2 infection, controlling virus replication, and preventing enhanced disease. Deficiency in type I interferon signaling results in dysregulated innate immune response to SARS-CoV-2 infection.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Virology
Rebecca Penn, John S. Tregoning, Katie E. Flight, Laury Baillon, Rebecca Frise, Daniel H. Goldhill, Cecilia Johansson, Wendy S. Barclay
Summary: Infections with highly pathogenic avian influenza viruses can cause severe disease due to excessive production of proinflammatory cytokines. Defective viral genomes (DVGs), which are generated during viral replication, can stimulate the immune response and alter the outcome of infection. This study found that the timing and levels of immunostimulatory DVGs are important factors in the pathogenesis of H5N1. Different levels of DVGs in virus stocks led to diverse outcomes in a mouse model, with high-DVG stocks causing mild disease and low-DVG stocks with accumulation of DVGs causing severe disease.
JOURNAL OF VIROLOGY
(2022)
Article
Immunology
Noam Kadouri, Tal Givony, Shir Nevo, Joschka Hey, Shifra Ben Dor, Golda Damari, Bareket Dassa, Jan Dobes, Dieter Weichenhan, Marion Bahr, Michelle Paulsen, Rebecca Haffner-Krausz, Marcus A. Mall, Christoph Plass, Yael Goldfarb, Jakub Abramson
Summary: This study reveals the importance of FOXN1 in the development of thymic epithelial cells and hair follicle cells, and identifies key regulatory regions and transcription factors involved in its expression.
SCIENCE IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
John S. Tregoning, David C. Stirling, Ziyin Wang, Katie E. Flight, Jonathan C. Brown, Anna K. Blakney, Paul F. McKay, Robert F. Cunliffe, Valarmathy Murugaiah, Christopher B. Fox, Mitchell Beattie, Ying K. Tam, Cecilia Johansson, Robin J. Shattock
Summary: To be effective, RNA vaccines require both in situ translation and the induction of an immune response to recruit cells to the site of immunization. These factors can pull in opposite directions with the inflammation reducing expression of the vaccine antigen. The study investigated how different formulations of self-amplifying RNA (saRNA) vaccines affect the systemic cytokine response and adaptive immune response to vaccination.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)