Review
Immunology
Shasha Chen, Zhiyong Liao, Pinglong Xu
Summary: Mitochondria play versatile roles in cellular processes and have emerged as critical components in innate immunity. This review provides a comprehensive exploration of the multifaceted mechanisms underlying the interactions between mitochondria and innate immune responses. It discusses the roles of healthy mitochondria as platforms for signalosome assembly, the release of mitochondrial components as signaling messengers, and the regulation of signaling via mitophagy. Additionally, it explores the impacts of mitochondrial proteins and metabolites on modulating innate immune responses, immune cell polarization, and their implications in infectious and inflammatory diseases.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yuanjiu Lei, Jordyn J. VanPortfliet, Yi-Fan Chen, Joshua D. Bryant, Ying Li, Danielle Fails, Sylvia Torres-Odio, Katherine B. Ragan, Jingti Deng, Armaan Mohan, Bing Wang, Olivia N. Brahms, Shawn D. Yates, Michael Spencer, Carl W. Tong, Marcus W. Bosenberg, Laura Ciaccia West, Gerald S. Shadel, Timothy E. Shutt, Jason W. Upton, Pingwei Li, A. Phillip West
Summary: Mitochondrial DNA (mtDNA) is a powerful activator of the innate immune system, and its specific immunostimulatory properties and detection by cytosolic nucleic acid sensors are still poorly understood. Our study demonstrates that mitochondrial genome instability leads to the accumulation of Z-form DNA. Z-DNA Binding Protein 1 (ZBP1) stabilizes Z-form mtDNA and forms a cytosolic complex with cGAS, RIPK1, and RIPK3, resulting in sustained phosphorylation of STAT1 and signaling of type I interferon (IFN-I). Increased levels of Z-form mtDNA, ZBP1 expression, and IFN-I signaling are observed in cardiomyocytes exposed to Doxorubicin, a commonly used chemotherapeutic drug that causes cardiotoxicity. Remarkably, mice lacking ZBP1 or IFN-I signaling are protected from Doxorubicin-induced cardiotoxicity. Our findings highlight ZBP1 as a potential therapeutic target in heart failure and other disorders where mtDNA stress contributes to interferon-related pathology.
Article
Virology
Dorian McIlroy, Cecile Peltier, My-Linh Nguyen, Louise Manceau, Lenha Mobuchon, Nicolas Le Baut, Ngoc-Khanh Nguyen, Minh-Chau Tran, The-Cuong Nguyen, Celine Bressollette-Bodin
Summary: Mutations in the BKPyV capsid accumulate in kidney transplant recipients, and are associated with neutralization escape. The mutations are mainly caused by cytosine deamination by APOBEC3A/B enzymes.
Article
Immunology
Xu Zhang, Yuru Wang, Pengtao Gong, Xiaocen Wang, Nan Zhang, Mengge Chen, Ran Wei, Xichen Zhang, Xin Li, Jianhua Li
Summary: This study investigated the host cell mitophagy induced by Neospora caninum and its role in parasite infection. The results showed that N. caninum can induce mitophagy in host cells and regulate the production of inflammatory cytokines. Promoting mitophagy worsened the parasite infection and inhibited the inflammatory response, while inhibiting mitophagy had the opposite effects.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Urology & Nephrology
Tobias F. Koyro, Emma Kraus, Sebastian Lunemann, Angelique Hoelzemer, Sonia Wulf, Johannes Jung, Pia Fittje, Florian Henseling, Christian Koerner, Tobias B. Huber, Adam Grundhoff, Thorsten Wiech, Ulf Panzer, Nicole Fischer, Marcus Altfeld
Summary: A recent study found that the activating natural killer cell receptor KIR3DS1 plays a protective role in controlling BK polyomavirus infection in the kidney, by regulating the interaction between HLA-F and KIR3DS1 to control disease progression, providing a rationale for exploring immunotherapeutic approaches for BK polyomavirus-associated nephropathy.
KIDNEY INTERNATIONAL
(2021)
Review
Immunology
Subhadip Choudhuri, Imran Hussain Chowdhury, Nisha Jain Garg
Summary: Innate immune cells, such as macrophages, serve as the first line of defense against pathogens. Pathogen invasion can impact mitochondrial metabolism in macrophages, influencing their response against pathogens. Mitophagy plays a critical role in regulating macrophage activation by removing damaged mitochondria.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hang Zhu, Ying Tan, Wenjun Du, Yang Li, Sam Toan, David Mui, Feng Tian, Hao Zhou
Summary: In the context of cardiac ischemia-reperfusion injury, PGAM5 plays a role in driving cardiomyocyte necroptosis by regulating mitochondrial quality control, while also suppressing necroptosis without preventing apoptosis, leading to improved heart function and reduced inflammation response.
Review
Biochemistry & Molecular Biology
Eva-Maria Eckl, Olga Ziegemann, Luisa Krumwiede, Evelyn Fessler, Lucas T. Jae
Summary: Mitochondrial fidelity is crucial for longevity and can be disrupted in various disease contexts. Tight homeostatic control and the activation of different mechanisms in response to stress are essential for maintaining mitochondrial function.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Parsa Alan, Kurt R. Vandevoorde, Bharat Joshi, Ben Cardoen, Guang Gao, Yahya Mohammadzadeh, Ghassan Hamarneh, Ivan R. Nabi
Summary: Mitochondria are a major source of reactive oxygen species (ROS) that are cytotoxic and contribute to cancer progression when uncontrolled. This study investigated the mechanisms underlying mitophagic control of mitochondrial homeostasis, and found that the E3 ubiquitin ligase Gp78 plays a role in promoting both basal and damage-induced mitophagy. Knockout of Gp78 increased mitochondrial volume and ROS production, and rendered cells resistant to mitophagy. This study highlights the importance of maintaining a healthy mitochondrial population in limiting ROS production and tumor cell proliferation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Virology
Nathan A. Krump, Ranran Wang, Wei Liu, June F. Yang, Tongcui Ma, Jianxin You
Summary: MCPyV, which can cause Merkel cell carcinoma, infects most humans asymptomatically. Understanding MCPyV biology and its interaction with host immune response may help develop targeted therapies for MCC. MCPyV replication induces an innate immune response, involving cGAS-STING, NF-kappa B, and IFI16 pathways.
JOURNAL OF VIROLOGY
(2021)
Article
Multidisciplinary Sciences
Esther B. Florsheim, Nathaniel D. Bachtel, Jaime L. Cullen, Bruna G. C. Lima, Mahdieh Godazgar, Fernando Carvalho, Carolina P. Chatain, Marcelo R. Zimmer, Cuiling Zhang, Gregory Gautier, Pierre Launay, Andrew Wang, Marcelo O. Dietrich, Ruslan Medzhitov
Summary: In addition to protecting the body from pathogens, the immune system can also affect behavior. In this study using mouse models of food allergy, it was found that allergic sensitization leads to antigen-specific avoidance behavior. The avoidance of allergens activates certain brain areas involved in aversive stimuli response. IgE antibodies and mast cells are necessary for allergen avoidance, and cysteinyl leukotrienes and growth and differentiation factor 15 play a role in promoting avoidance. Genetic background also influences avoidance behavior. These findings suggest that antigen-specific behavioral modifications may have evolved to avoid unfavorable environments.
Article
Cell Biology
Hyejin Kim, Ah-Young Kim, Jieun Choi, Sun Young Park, Sang Hyun Park, Jae-Seok Kim, Sim-In Lee, Jong-Hyeon Park, Choi-Kyu Park, Young-Joon Ko
Summary: During foot-and-mouth disease virus (FMDV) infection, inhibition of MDA5 protein expression is primarily caused by the non-structural proteins Lb(pro) and 3C(pro), with 3C(pro) directly interacting with MDA5 protein through its protease activity. This study sheds light on the pathogenesis of FMDV and may contribute to the development of novel vaccines or therapeutic agents.
Editorial Material
Cell Biology
Yu Young Jeong, Nuo Jia, Dhasarathan Ganesan, Qian Cai
Summary: Mitochondrial defects and phosphorylated MAPT/tau induce mitochondrial damage and activate mitophagy, which depletes mitochondria from synaptic terminals and impairs synaptic function. Increasing RHOT1 levels can reverse cognitive impairment and prevent synapse loss in tauopathy mice.
Editorial Material
Cell Biology
Samuel A. Killackey, Yuntian Bi, Dana J. Philpott, Damien Arnoult, Stephen E. Girardin
Summary: Mitochondrial protein import stress has been identified as a potential common trigger for mitophagy, offering new avenues for therapeutic exploration and mechanistic insights.
Article
Immunology
Na Zhang, Fei Wang, Gaomeng Zhang, Qi Zhang, Yuhong Liu, Qiao Wang, Mohamed Shafey Elsharkawy, Maiqing Zheng, Jie Wen, Guiping Zhao, Qinghe Li
Summary: Toll-like receptors (TLRs) are important immune sensors involved in host defense. In this study, the researchers discovered that the deubiquitinase USP7 interacts with MyD88 protein, regulating its expression and participating in bacteria-induced inflammation. This finding contributes to our understanding of the regulatory mechanisms in immune signaling.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Simone Cesaro, Per Ljungman, Malgorzata Mikulska, Hans H. Hirsch, Marie Von Lilienfeld-Toal, Catherine Cordonnier, Sylvain Meylan, Varun Mehra, Jan Styczynski, Francesco Marchesi, Caroline Besson, Fausto Baldanti, Raul Cordoba Masculano, Gernot Beutel, Herman Einsele, Elie Azoulay, Johan Maertens, Rafael de la Camara, Livio Pagano
Summary: SARS-CoV-2 infection can lead to severe outcomes in immunocompromised hematological patients, with high mortality rates observed. Treatment strategies focus on controlling viral replication and inflammation. However, the effectiveness and benefits of preventive and therapeutic measures in hematological patients require further investigation.
Article
Immunology
Astrid Beerlage, Karoline Leuzinger, Luca Valore, Roby Mathew, Till Junker, Beatrice Drexler, Jakob R. Passweg, Hans H. Hirsch, Joerg Halter
Summary: Patients after allogeneic stem cell transplantation generally have a good response to mRNA vaccines against SARS-CoV-2, but there is still a proportion of patients with inadequate vaccination response, which can be improved after a third vaccination despite immunosuppressive therapy.
TRANSPLANT INFECTIOUS DISEASE
(2022)
Letter
Immunology
Maddalena Peghin, Hans H. Hirsch
Article
Immunology
Cedric Hirzel, Lea Projer, Andrew Atkinson, Bernard Surial, Nicolas J. Mueller, Oriol Manuel, Matteo Mombelli, Christian van Delden, Hans H. Hirsch, Katia Boggian, Laura N. Walti, Daniel Sidler, Karine Hadaya, Michael Dickenmann, Thomas F. Muller, Isabelle Binet, Dela Golshayan, Uyen Huynh-Do
Summary: The burden of infections during the first year posttransplant is high but not significantly different in ABOi-KT and ABOc-KT recipients, suggesting that concerns regarding infectious complications should not affect the implementation of ABOi-KT programs.
Article
Critical Care Medicine
Andrei M. Darie, Nina Khanna, Kathleen Jahn, Michael Osthoff, Stefano Bassetti, Mirjam Osthoff, Desiree M. Schumann, Werner C. Albrich, Hans Hirsch, Martin Brutsche, Leticia Grize, Michael Tamm, Daiana Stolz
Summary: Multiplex bacterial PCR examination of bronchoalveolar lavage decreases the duration of inappropriate antibiotic therapy in patients with pneumonia.
LANCET RESPIRATORY MEDICINE
(2022)
Article
Microbiology
Jelissa Katharina Peter, Fanny Wegner, Severin Gsponer, Fabrice Helfenstein, Tim Roloff, Rahel Tarnutzer, Kerstin Grosheintz, Moritz Back, Carla Schaubhut, Sabina Wagner, Helena M. B. Seth-Smith, Patrick Scotton, Maurice Redondo, Christiane Beckmann, Tanja Stadler, Andrea Salzmann, Henriette Kurth, Karoline Leuzinger, Stefano Bassetti, Roland Bingisser, Martin Siegemund, Maja Weisser, Manuel Battegay, Sarah Tschudin Sutter, Aitana Lebrand, Hans H. Hirsch, Simon Fuchs, Adrian Egli
Summary: Breakthrough infections in fully vaccinated individuals are rare and mild, but can occur early post-vaccination. Lower risk factors include age and previous COVID-19 infection, while higher risk factors include vaccination with Pfizer/BioNTech, chronic disease, and being a healthcare worker. Continuous monitoring of breakthrough infections is crucial due to emerging new variants.
Letter
Immunology
Hans H. Hirsch, Michael Mengel, Nassim Kamar
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Immunology
Karoline Leuzinger, Amandeep Kaur, Maud Wilhelm, Konstantin Frank, Caroline A. Hillenbrand, Fabian H. Weissbach, Hans H. Hirsch
Summary: In this study, the replication of BK polyomavirus (BKPyV) was found to be associated with failing immune control and BKPyV-associated hemorrhagic cystitis in allogeneic hematopoietic cell transplantation (HCT). Molecular markers of BKPyV replication and disease were identified through quantitative nucleic acid testing (QNAT), DNase-I treatment, next-generation sequencing (NGS), and cell-mediated immunity testing. The fragmentation of BKPyV genome below 250 bp was found to impair the detection of BKPyV diversity and genotype-associated changes involved in immune escape.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Immunology
Marco Labarile, Tom Loosli, Marius Zeeb, Katharina Kusejko, Michael Huber, Hans H. Hirsch, Matthieu Perreau, Alban Ramette, Sabine Yerly, Matthias Cavassini, Manuel Battegay, Andri Rauch, Alexandra Calmy, Julia Notter, Enos Bernasconi, Christoph Fux, Huldrych F. Gunthard, Chloe Pasin, Roger D. Kouyos
Summary: This study investigated and predicted the dynamics of HIV transmission in Switzerland using a network-based clustering method and statistical learning approaches. The study found that network characteristics can capture major heterogeneities in transmission and that cluster structure has the potential for real-time prediction of ongoing transmission.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Virology
Klaudia Naegele, Fabian H. Weissbach, Karoline Leuzinger, Rainer Gosert, Lukas Bubendorf, Hans H. Hirsch
Summary: HPV infections are often asymptomatic, but certain genotypes can lead to cervical cancer. This study compared different nucleic acid extraction methods for detecting and genotyping HPV in cervical swabs with atypical cells. The results showed that centrifugation/enrichment improved HPV detection and genotyping accuracy. As multivalent HPV vaccine coverage increases, it is important to improve extraction methods and broaden genotype coverage to accurately detect the evolving HPV virome.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Urology & Nephrology
Patricia Hirt-Minkowski, Joelle Handschin, Susanne Stampf, Helmut Hopfer, Thomas Menter, Lisa Senn, Gideon Hoenger, Caroline Wehmeier, Patrizia Amico, Jurg Steiger, Michael Koller, Michael Dickenmann, Stefan Schaub
Summary: This study aimed to investigate the clinical utility of urine CXCL10 monitoring in renal allografts. The results showed that urine CXCL10 monitoring did not have a significant beneficial effect on 1-year outcomes in renal transplantation.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Virology
Karoline Leuzinger, Hans H. Hirsch
Summary: Management of cytomegalovirus (CMV) in transplant patients relies on measuring plasma CMV-loads. The comparison between automated Roche-cobas (R) 6800-CMV and Roche-CAP/CTM-CMV with laboratory-developed Basel-CMV-UL54-95bp and Basel-CMV-UL111a-77bp showed qualitative concordance. DNase-I treatment significantly reduced CMV-loads for all assays. Non-encapsidated fragmented CMV-DNA is the major form of plasma CMV-loads measured by fully-automated platforms.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Letter
Oncology
Simone Cesaro, Malgorzata Mikulska, Hans H. Hirsch, Jan Styczynski, Sylvain Meylan, Catherine Cordonnier, Davide Navarro, Marie von Lilienfeld-Toal, Varun Mehra, Francesco Marchesi, Caroline Besson, Raul Cordoba Masculano, Gernot Beutel, Herman Einsele, Johan Maertens, Rafael de la Camara, Per Ljungman, Livio Pagano
Article
Hematology
Firas El Chaer, Daniel R. Kaul, Janet A. Englund, Michael Boeckh, Marjorie V. Batista, Susan K. Seo, Paul A. Carpenter, David Navarro, Hans H. Hirsch, Michael G. Ison, Genovefa A. Papanicolaou, Roy F. Chemaly
Summary: The Practice Guidelines Committee of the American Society of Transplantation and Cellular Therapy partnered with its Transplant Infectious Disease Special Interest Group to update the guidelines for hematopoietic cell transplantation. They adopted a new approach of publishing each topic in a concise format of FAQs, tables, and figures. In the seventh guideline, they focused on respiratory syncytial virus (RSV) and provided answers to FAQs regarding epidemiology, clinical diagnosis, prophylaxis, and treatment.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
Meeting Abstract
Medicine, General & Internal
K. Leuzinger, K. Frank, F. H. Weissbach, B. Oettli, M. Wilhelm, A. Kaur, H. H. Hirsch
SWISS MEDICAL WEEKLY
(2022)
