Article
Microbiology
Melissa Berni, Luca Bolzoni, Ilaria Menozzi, Alessandra Dodi, Chiara Bracchi, Marina Morganti, Erika Scaltriti, Stefano Pongolini, Martina Tambassi
Summary: This study reveals that a significant portion of the global population of Salmonella Derby is evolving to adapt to the swine host while simultaneously attenuating its virulence for humans. The fixation of deleterious mutations in the SPI-1 genes plays a key role in this process. The study provides insights into the molecular mechanisms underlying the ecology and host adaptation of Salmonella.
MICROBIOLOGY SPECTRUM
(2023)
Article
Oncology
Mirela Kremenovic, Alfred A. Chan, Bing Feng, Lukas Baeriswyl, Steve Robatel, Thomas Gruber, Li Tang, Delphine J. Lee, Mirjam Schenk
Summary: In this study, a novel BCG lysate was developed and formulated into a thermosensitive hydrogel. The BCG lysate exhibited enhanced antitumor efficacy and promoted a proinflammatory tumor microenvironment in vivo. The underlying mechanisms of BCG lysate-mediated tumor immunity relied on macrophages (M phi) and dendritic cells (DCs). The BCG hydrogel treatment induced systemic immunity, suppressed lung metastases, and improved survival in melanoma-bearing mice. Furthermore, BCG hydrogel treatment enhanced antigen processing and presentation, and increased the frequency of melanoma-reactive CD8(+) T cells. In human melanoma patients, intralesional-BCG treatment was associated with enhanced M1 M phi, mature DCs, antigen processing and presentation, and increased patient survival.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Payton L. Marshall, Nadine Nagy, Gernot Kaber, Graham L. Barlow, Amrit Ramesh, Bryan J. Xie, Miles H. Linde, Naomi L. Haddock, Colin A. Lester, Quynh-Lam Tran, Christiaan R. de Vries, Aviv Hargil, Andrey V. Malkovskiy, Irina Gurevich, Hunter A. Martinez, Hedwich F. Kuipers, Koshika Yadava, Xiangyue Zhang, Stephen P. Evanko, John A. Gebe, Xi Wang, Robert B. Vernon, Carol de la Motte, Thomas N. Wight, Edgar G. Engleman, Sheri M. Krams, Everett H. Meyer, Paul L. Bollyky
Summary: Treatment with 4-methylumbelliferone (4MU) reduces pericellular hyaluronan, disrupts interactions between DC and T-cells, and inhibits T-cell proliferation. 4MU can delay rejection of allogeneic pancreatic islet and cardiac transplants, as well as suppress allogeneic T-cell activation.
Review
Immunology
Takumi Kawasaki, Moe Ikegawa, Taro Kawai
Summary: The lungs have an immune defense mechanism that uses various cells to eliminate harmful pathogens and activate T cell immune response. In addition to immune cells, other lung cells also participate in antigen presentation and T cell activation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Chao Pan, Lu Wang, Mengmeng Zhang, Juanjuan Li, Junqiu Liu, Jinyao Liu
Summary: Introduces a new immunization strategy called in situ polymerization-mediated antigen presentation (IPAP), which allows antigen-loaded nanovaccines to spontaneously form and efficiently anchor onto dendritic cells in vivo through co-deposition with dopamine. IPAP promotes antigen presentation by increasing cell uptake and reducing antigen degradation. It prolongs antigen duration and enhances accumulation in lymph nodes, resulting in strong antigen-specific immune responses. IPAP is applicable for different antigens and overcomes the disadvantages of complex preparation and purification processes.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Oncology
Tim B. Fessenden, Lauren E. Stopfer, Fiona Chatterjee, Julian Zulueta, Josh Mesfin, Therese Cordero Dumit, Irene Reijers, Esmee P. Hoefsmit, Christian Blank, Forest White, Stefani Spranger
Summary: Cytotoxic CD8(+) T cells must recognize tumor-derived antigens to achieve effective tumor elimination. Our study shows that dendritic cells induce cytotoxic CD8(+) T-cell responses by cross-presenting tumor-derived peptides, and the proportion of membrane-derived neoantigens is associated with reduced survival and treatment response.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Chemistry, Multidisciplinary
Hejin Jiang, Rui Liu, Lu Wang, Xinyue Wang, Mengmeng Zhang, Sisi Lin, Zhenping Cao, Feng Wu, Yingbin Liu, Jinyao Liu
Summary: Chirality plays a critical role in biological systems, and this study demonstrates the potential of using supramolecular chiral polymer micelles (SCPMs) to activate the immune system for disease prevention and treatment.
ADVANCED MATERIALS
(2023)
Article
Veterinary Sciences
Jwerlly Tatiana Pico-Rodriguez, Hugo Martinez-Jarquin, Jose de Jesus Gomez-Chavez, Mireya Juarez-Ramirez, Luary Carolina Martinez-Chavarria
Summary: The study aimed to evaluate the effect of deleting SPI-1 or SPI-2 genes on intestinal and systemic salmonellosis using the avian model. The results showed that the deletion of these genes attenuated the virulence and reduced the survival ability of bacteria in the intestine and liver.
VETERINARY RESEARCH COMMUNICATIONS
(2023)
Article
Chemistry, Physical
Jilong Wang, Mengwen Huang, Senbiao Chen, Yingli Luo, Song Shen, Xiaojiao Du
Summary: This study developed an effective immunotherapy strategy to improve tumor treatment by enhancing the maturation of DCs and antigen presentation, leading to improved efficacy against poorly immunogenic tumors.
Article
Immunology
Hsin-Hung Lin, Hsiu-Ling Chen, Chang-Ching Weng, Rajendra Prasad Janapatla, Chyi-Liang Chen, Cheng-Hsun Chiu
Summary: The study revealed that Salmonella induces apoptosis in macrophages through caspase-3 activation, especially via the expression of SPI-1 structure proteins and effectors. This mechanism may help explain why Salmonella infections in children often present as mild bacteremia with less systemic inflammatory response.
JOURNAL OF MICROBIOLOGY IMMUNOLOGY AND INFECTION
(2021)
Review
Immunology
Ray A. Ohara, Kenneth M. Murphy
Summary: Cross-priming, initially recognized in cytotoxic T lymphocyte (CTL) responses, involves the presentation of minor histocompatibility antigens by antigen presenting cells (APCs) derived from immunizing cells. As understanding of T cell receptor antigen recognition progressed, cross-priming was redefined as cross-presentation and expanded to include different forms of antigens and APCs not involved in in vivo CTL priming. In vitro cell models have been utilized for studying cross-presentation, but recent studies have shown differences between these models and in vivo APCs. Current research focuses on validating in vivo pathways and gene candidates for cross-presentation, and evaluating their contributions to CTL responses across different antigens and immunologic settings.
SEMINARS IN IMMUNOLOGY
(2023)
Article
Oncology
Gi-Hoon Nam, Minsu Kwon, Hanul Jung, Eunbyeol Ko, Seong A. Kim, Yoonjeong Choi, Su Jeong Song, Seohyun Kim, Yeji Lee, Gi Beom Kim, Jihoon Han, Jiwan Woo, Yakdol Cho, Cherlhyun Jeong, Seung-Yoon Park, Thomas M. Roberts, Yong Beom Cho, In-San Kim
Summary: The study shows that statins can enhance the immunogenicity of KRAS-mutant tumors by inducing immunogenic cell death and enhancing the cross-priming ability of dendritic cells, thereby stimulating CD8+ T-cell immune responses against the tumors. Combination therapy using statins and other agents can significantly increase the immunogenicity of KRAS(mut) tumors and improve tumor-specific immunity, overcoming resistance to PD-1 blockade therapies and increasing survival rates in KRAS(mut) tumor models.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Cell Biology
Ryosuke Tashiro, Kuniyasu Niizuma, Jun Kasamatsu, Yuko Okuyama, Sherif Rashad, Atsuo Kikuchi, Miki Fujimura, Shigeo Kure, Naoto Ishii, Teiji Tominaga
Summary: The study found that RNF213 plays a critical role in antigen uptake, processing, and presentation, with Rnf213-KO and Rnf213-KI mice experiments showing that RNF213 deficiency leads to decreased antigen uptake and processing capabilities, resulting in the inability to effectively activate antigen-specific T cells.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ju-Sim Kim, Lin Liu, Bennett Davenport, Sashi Kant, Thomas E. Morrison, Andres Vazquez-Torres
Summary: Salmonella protects itself from the killing effect of reactive oxygen species (ROS) produced by host cells by activating the transcription of SPI-2 genes.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Microbiology
Seul Kim, Eunsuk Kim, Hyunjin Yoon
Summary: Salmonella alters cellular processes to improve intracellular fitness during host infection by rewiring cellular transcriptional regulation through alternative sigma factors such as rpoS. Deprivation of outer membrane protein YcfR in Salmonella Typhimurium leads to decreased intracellular survival and downregulation of SPI-2 genes, which is abolished in the absence of rpoS. RpoS-associated stress responses in Salmonella due to impaired envelope integrity may reciprocally downregulate the expression of SPI-2 genes to reduce its virulence.
FRONTIERS IN MICROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Alexander Kehl, Janina Noster, Michael Hensel
TRENDS IN MICROBIOLOGY
(2020)
Article
Cell Biology
Marc Schulte, Katharina Olschewski, Michael Hensel
Summary: Intracellular bacteria such as Salmonella enterica face various defense mechanisms from their mammalian host cells, and the ability to sense and respond to these damages is crucial for survival. By using fluorescence protein reporter strains, researchers were able to monitor stress responses and proliferation of single bacterial cells, leading to the detection and quantification of distinct subpopulations with varying levels of stress response and proliferation within S. enterica.
CELLULAR MICROBIOLOGY
(2021)
Article
Microbiology
Emiliano Cohen, Shalevet Azriel, Oren Auster, Adiv Gal, Carmel Zitronblat, Svetlana Mikhlin, Felix Scharte, Michael Hensel, Galia Rahav, Ohad Gal-Mor
Summary: Salmonella enterica is a highly diverse bacterial pathogen that infects humans and animals. While many serovars of S. enterica have a broad host specificity, some pathotypes have evolved to cause disease in limited host species. The mechanisms underlying the host specificity of Salmonella are not fully understood. This study provides genetic analysis, phenotypic characterization, and virulence profiling of a monophasic S. enterica serovar Typhimurium strain isolated from wild sparrows in Israel, revealing unique genetic features and phenotypic profiles that contribute to its adaptation to birds.
Article
Biology
Marc Schulte, Katharina Olschewski, Michael Hensel
Summary: The study demonstrates that non-replicating Salmonella enterica serovar Typhimurium persisters, which are tolerant to antibiotics, can sense their environment and respond to stressors. This suggests that stress sensing and response of persisters may be targeted as an antimicrobial strategy.
COMMUNICATIONS BIOLOGY
(2021)
Article
Cell Biology
Jennifer Roder, Pascal Felgner, Michael Hensel
Summary: This study used bacteria with reporter plasmids to investigate environmental cues acting on Salmonella enterica serovar Typhimurium (STM) within host cells, revealing that P-i concentration in the Salmonella-containing vacuole (SCV) is limiting and P-i limitation increases with bacterial proliferation. It was also observed that STM in the host cell cytosol did not face P-i limitations. Additionally, the activity of SPI2-T3SS relieved P-i limitation in the SCV.
CELLULAR MICROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Malte Kellermann, Felix Scharte, Michael Hensel
Summary: Pathogenic intracellular microorganisms manipulate host cells to create niches for survival and replication. This review focuses on the manipulation of organelle compartments by pathogens and highlights the specific interactions of different pathogens with host cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Microbiology
Tatjana Reuter, Felix Scharte, Rico Franzkoch, Viktoria Liss, Michael Hensel
Summary: Typhoidal Salmonella enterica serovars manipulate host cells actively with a stealth strategy, deploying SPI2-T3SS for proliferation in epithelial cells but not for survival or proliferation in phagocytic host cells. The reduced intracellular activities of STY and SPA contribute to systemic spread and persistence of these pathogens.
Article
Immunology
Jacob Cobb, Jeffrey Rawson, Nelson Gonzalez, Michael Hensel, Fouad Kandeel, Mohamed I. Husseiny
Summary: The oral vaccine combination therapy successfully prevented and reversed type 1 diabetes in non-obese diabetic mice, with the alternative carrier strain Delta msbB showing lower pathogenic side effects and higher rates of host cell infection. This further demonstrates the potential of an oral Salmonella-based combined therapy in the treatment of early T1D.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Patrick Niekamp, Felix Scharte, Tolulope Sokoya, Laura Vittadello, Yeongho Kim, Yongqiang Deng, Elisabeth Sudhoff, Angelika Hilderink, Mirco Imlau, Christopher J. Clarke, Michael Hensel, Christopher G. Burd, Joost C. M. Holthuis
Summary: Cells use a sphingomyelin-based lysosomal repair pathway to reverse potentially lethal membrane damage, independently of ESCRT function. Activation of scramblases, sphingomyelin, and neutral sphingomyelinases helps preserve the functional integrity of lysosomes.
NATURE COMMUNICATIONS
(2022)
Article
Microbiology
Helit Cohen, Claire Hoede, Felix Scharte, Charles Coluzzi, Emiliano Cohen, Inna Shomer, Ludovic Mallet, Sebastien Holbert, Remy Felix Serre, Thomas Schiex, Isabelle Virlogeux-Payant, Guntram A. Grassl, Michael Hensel, Helene Chiapello, Ohad Gal-Mor
Summary: Salmonella enterica includes various serovars causing distinct diseases in humans. In this study, we compared the global gene expression and intracellular phenotypes of S. Typhimurium (STM) and S. Paratyphi A (SPA), representative serovars of non-typhoidal and typhoidal Salmonella, during human epithelial cell infection. We found different expression patterns in key virulence and metabolic pathways, cytosolic motility, and reinvasion ability of SPA after exiting infected cells. These differences may contribute to the invasive and systemic disease developed following SPA infection in humans.
Article
Biochemical Research Methods
Laura Elpers, Joerg Deiwick, Michael Hensel
Summary: This study provides initial insights into the complex adaptation of STM to different environmental temperatures and reveals that STM can infect not only mammalian hosts but also enter new infection routes. This has important implications for investigating global virulence factors, their impact on infection routes, and potential anti-infective strategies.
MOLECULAR & CELLULAR PROTEOMICS
(2022)
Article
Microbiology
Laura Elpers, Lena Lueken, Fabio Lange, Michael Hensel
Summary: The number of outbreaks caused by gastrointestinal pathogens associated with produce is increasing. The mechanisms involved in the colonization, persistence, and transmission of these pathogens on fresh produce are poorly understood. This study focused on the adhesive factors of S. enterica serovar Typhimurium on butterhead lettuce (Lactuca sativa) and identified several factors that contribute to its adhesion to lettuce leaves.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biochemistry & Molecular Biology
Felix Scharte, Rico Franzkoch, Michael Hensel
Summary: Salmonella enterica is a foodborne pathogen causing different diseases in humans. The mechanism of invasion and dissemination of typhoidal and non-typhoidal serovars are different. SPA exhibits cytosolic motility mediated by flagella, which allows it to evade xenophagy and contribute to the dissemination of systemic infection. This study used single-cell microscopy to analyze the triggers and cellular consequences of cytosolic motility.
MOLECULAR MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Vera Goser, Nathalie Sander, Marc Schulte, Felix Scharte, Rico Franzkoch, Viktoria Liss, Olympia E. E. Psathaki, Michael Hensel
Summary: Salmonella enterica remodels the host endosomal system to create a specific intracellular niche for survival and proliferation. Translocated effectors interact with endosomal vesicles, continuously fusing with Salmonella-containing vacuoles and induced filaments to ensure bacterial survival and proliferation.
NATURE COMMUNICATIONS
(2023)
Article
Gastroenterology & Hepatology
Marcus Fulde, Kira van Vorst, Kaiyi Zhang, Alexander J. Westermann, Tobias Busche, Yong Chiun Huei, Katharina Welitschanski, Isabell Froh, Dennis Paegelow, Johanna Plendl, Christiane Pfarrer, Jorn Kalinowski, Jorg Vogel, Peter Valentin-Weigand, Michael Hensel, Karsten Tedin, Urska Repnik, Mathias W. Hornef
Summary: The study suggests that SPI2 T3SS effector molecules contribute to the apical to basolateral transmigration of Salmonella-containing vacuoles during the early stage of infection in the intestinal epithelium. Contrary to expectations, infection with SPI2 T3SS mutants results in significantly enlarged intraepithelial Salmonella-containing vacuoles with altered cellular positioning.