Article
Immunology
Deepthi Shankaran, Prabhakar Arumugam, Ragavendran P. Vasanthakumar, Anjali Singh, Ankur Bothra, Sheetal Gandotra, Vivek Rao
Summary: During infections, host phagocytes use metabolic shuffling to restrict invading pathogens, but this plasticity also allows pathogens to manipulate them. In the case of Mycobacterium tuberculosis infection, clinical lineages of the bacteria can induce a strong and early type I interferon response, leading to increased expression of IL-6 and improved intracellular survival.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Cell Biology
Patience Shumba, Thomas Sura, Kirsten Moll, Bhavya Chakrakodi, Lea Toelken, Joern Hossmann, Katharina Hoff, Ole Hyldegaard, Michael Nekludov, Mattias Svensson, Per Arnell, Steinar Skrede, Nikolai INFECT Study Group, Anna Norrby-Teglund, Nikolai Siemens
Summary: In this study, it was found that tissue inflammation, neutrophil influx, and degranulation positively correlate with increasing frequency of SpeB-negative GAS clones in patients with monomicrobial necrotizing soft tissue infections. Single colony proteomics revealed that GAS isolated directly from tissue express but do not secrete SpeB. These findings provide new information about GAS fitness and heterogeneity in the soft tissue milieu.
JOURNAL OF BIOMEDICAL SCIENCE
(2023)
Article
Immunology
Maud Tusseau, Ema Lovsin, Charlotte Samaille, Remi Pescarmona, Anne-Laure Mathieu, Maria-Cristina Maggio, Velma Selmanovic, Marusa Debeljak, Angelique Dachy, Gregor Novljan, Alexandre Janin, Louis Januel, Jean-Baptiste Gibier, Emilie Chopin, Isabelle Rouvet, David Goncalves, Nicole Fabien, Gillian Rice, Gaetan Lesca, Audrey Labalme, Paola Romagnani, Thierry Walzer, Sebastien Viel, Magali Perret, Yanick J. Crow, Tadej Avcin, Rolando Cimaz, Alexandre Belot
Summary: The interferon signaling in DNASE1L3 deficient patients is transient, unlike the anomalies observed in other diseases. DNASE1L3 deficiencies are associated with a broad phenotype including lupus nephritis and hypocomplementemic urticarial vasculitis.
JOURNAL OF CLINICAL IMMUNOLOGY
(2022)
Article
Immunology
Andrea L. Herrera, Rashaun Potts, Victor C. Huber, Michael S. Chaussee
Summary: Respiratory influenza virus infection increases the likelihood and severity of systemic group A streptococcus (GAS) diseases, even when GAS infection does not originate in the respiratory tract.
Article
Pediatrics
Lauri Ivaska, Jussi Niemela, Kirsi Grondahl-Yli-Hannuksela, Niina Putkuri, Jaana Vuopio, Tytti Vuorinen, Matti Waris, Kaisu Rantakokko-Jalava, Ville Peltola
Summary: The aim of this study was to investigate the detection of group A streptococcus (GAS) in pediatric pharyngitis patients using different diagnostic methods. The study found that GAS was frequently detected even in pediatric pharyngitis patients with a confirmed viral infection. This suggests that viral infections may lead to incidental carriage of GAS in the throat.
EUROPEAN JOURNAL OF PEDIATRICS
(2022)
Article
Microbiology
Stephan Brouwer, Magnus G. Jespersen, Cheryl-Lynn Y. Ong, David M. P. De Oliveira, Bernhard Keller, Amanda J. Cork, Karrera Y. Djoko, Mark R. Davies, Mark J. Walker
Summary: In this study, the researchers found that the ABC transporter substrate binding protein GshT is a crucial component of the glutathione salvage pathway in glutathione-auxotrophic GAS. Host-acquired glutathione is essential for the GAS antioxidant defense system, enabling it to evade the host innate immune response. This study provides mechanistic insights into how extracellular bacterial pathogens like GAS exploit host glutathione for their own benefit.
Article
Cardiac & Cardiovascular Systems
Henry M. Vu, Daniel E. Hammers, Zhong Liang, Gabrielle L. Nguyen, Mary E. Benz, Thomas E. Moran, Dustin L. Higashi, Claudia J. Park, Yetunde A. Ayinuola, Deborah L. Donahue, Ana L. Flores-Mireles, Victoria A. Ploplis, Francis J. Castellino, Shaun W. Lee
Summary: The study delves into the mechanisms of colonization and dissemination of Group A Streptococcus infections, revealing the significant roles of SK and PAM in the process of epithelial wound retraction, as well as the crucial factor of fibrin clot dissolution.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Robert S. Hagan, John C. Gomez, Jose Torres-Castillo, Jessica R. Martin, Claire M. Doerschuk
Summary: Bacterial pneumonia leads to the recruitment and activation of neutrophils and macrophages in the lung, which contribute to antibacterial defenses. TBK1, a protein with multiple functions, is found to play a role in antibacterial defenses in the lung apart from its known functions. TBK1 deficiency leads to impaired bacterial clearance and survival, and lower cytokine expression in the infected lung. Neutrophils, but not macrophages, are identified as the key TBK1-dependent cell type in this process.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Chunlei Jiao, Sahil Sharma, Gaurav Dugar, Natalia L. Peeck, Thorsten Bischler, Franziska Wimmer, Yanying Yu, Lars Barquist, Christoph Schoen, Oliver Kurzai, Cynthia M. Sharma, Chase L. Beisel
Summary: The study found that tracrRNA hybridizing with cellular RNAs can lead to the formation of new crRNAs capable of guiding DNA targeting by Cas9. Reprogrammed tracrRNAs linking the presence of RNA of interest to DNA targeting were used in the LEOPARD diagnostic platform, allowing simultaneous detection of RNAs from different viruses in one test.
Article
Infectious Diseases
Loraine V. Fabri, Kristy I. Azzopardi, Joshua Osowicki, Hannah R. Frost, Pierre R. Smeesters, Andrew C. Steer
Summary: A reliable molecular method has been developed for measuring Streptococcus pyogenes bacterial load from throat swabs collected in a controlled human infection model of S. pyogenes pharyngitis.
BMC INFECTIOUS DISEASES
(2021)
Article
Microbiology
Henry H. Le, Min-Ting Lee, Kevin R. Besler, Elizabeth L. Johnson
Summary: Microbially-derived gut metabolites play an important role in host phenotypes. This study traces bacterial sphingolipids from gut symbiont Bacteroides thetaiotaomicron to mouse colons and livers, and finds that bacterial sphingolipid synthesis can rescue excess lipid accumulation in a mouse model of hepatic steatosis. The transfer of this sphingolipid to the liver potentially contributes to microbiota-mediated liver function.
CELL HOST & MICROBE
(2022)
Article
Medicine, General & Internal
Sanjeevan Jahagirdar, Lorna Morris, Nirupama Benis, Oddvar Oppegaard, Mattias Svenson, Ole Hyldegaard, Steinar Skrede, Anna Norrby-Teglund, Vitor A. P. Martins dos Santos, Edoardo Saccenti
Summary: The study revealed specific responses in host-pathogen interactions of NSTI patients, including S. pyogenes and polymicrobial infections. By studying individual networks of different patient groups, different modes of entry and immune evasion strategies were identified.
Article
Microbiology
Sruti DebRoy, William C. Shropshire, Chau Nguyen Tran, Haiping Hao, Marc Gohel, Jessica Galloway-Pena, Blake Hanson, Anthony R. Flores, Samuel A. Shelburne
Summary: This study focused on the impact of the core chromosomal type I restriction modification (RM) system on DNA methylation in beta-hemolytic streptococci, revealing that its primary role is immunity against exogenous DNA rather than affecting the expression of the key multigene activator protein (Mga) or Mga-regulated genes.
Article
Immunology
Dylan Minor, Jacob Cavon, Thea Johnson, Savannah Ontiveros, Daniel Gao, Mark T. Quinn, Benfang Lei
Summary: In this study, we investigated whether MyD88 KO mice were susceptible to acute group A Streptococcus (GAS) infection through transmission. We found that MyD88(-/-) recipient mice had increased GAS loads in the nasal cavity and throat and became moribund after commingling with GAS-infected mice. Furthermore, we observed that MyD88 signaling is critical for protection of the respiratory tract lamina propria but not nasal and nasopharyngeal epithelia against GAS infection.
INFECTION AND IMMUNITY
(2022)
Article
Multidisciplinary Sciences
Arvind Yerramilli, Asha C. Bowen, Adrian J. Marcato, Jodie McVernon, Jonathan R. Carapetis, Patricia T. Campbell, Steven Y. C. Tong
Summary: This study used clinical data of skin sores in Aboriginal children to provide a detailed description of the anatomical locations of these sores. The results showed that skin sores predominantly occurred in exposed areas such as the lower limbs and distal upper limbs, with distribution varying by age group and causative pathogen.
Article
Allergy
Philipp Starkl, Nicolas Gaudenzio, Thomas Marichal, Laurent L. Reber, Riccardo Sibilano, Martin L. Watzenboeck, Frederic Fontaine, Andre C. Mueller, Mindy Tsai, Sylvia Knapp, Stephen J. Galli
Summary: The study found that IgE sensitization enhances MC detoxification of honeybee venom by promoting proteolytic degradation and heparin-related interference with toxicity. This research emphasizes the importance of IgE, MCs, and specific MC products in defense against honeybee venom.
Article
Respiratory System
Martin L. Watzenboeck, Anna-Dorothea Gorki, Federica Quattrone, Riem Gawish, Stefan Schwarz, Christopher Lambers, Peter Jaksch, Karin Lakovits, Sophie Zahalka, Nina Rahimi, Philipp Starkl, Doerte Symmank, Tyler Artner, Celine Pattaroni, Nikolaus Fortelny, Kristaps Klavins, Florian Frommlet, Benjamin J. Marsland, Konrad Hoetzenecker, Stefanie Widder, Sylvia Knapp
Summary: Lung transplantation is the ultimate treatment option for patients with end-stage respiratory diseases, but the mortality rate is high due to chronic lung allograft dysfunction (CLAD). The mechanisms leading to CLAD are not well understood due to insufficient understanding of post-transplant adaptation processes. This study analyzed bronchoalveolar lavage samples from lung recipients and donors, and found that recipient-specific and environmental factors shape the long-term lung microbiome. Certain bacterial strains were found to be correlated with underlying lung diseases even after transplantation. Machine learning techniques accurately predicted future changes in lung function, with the microbial profiles showing high predictive power. The study highlights the importance of understanding lung adaptation processes and the role of microbiome in predicting allograft function.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Anna-Dorothea Gorki, Dorte Symmank, Sophie Zahalka, Karin Lakovits, Anastasiya Hladik, Brigitte Langer, Barbara Maurer, Veronika Sexl, Renate Kain, Sylvia Knapp
Summary: This study proposes a novel culture model for studying and expanding murine primary alveolar macrophages (AMs) in vitro over several months. The cultured AMs maintain typical features and surface markers, and exhibit similar functions and transcriptional profile to primary AMs. When transferred into AM-deficient mice, the cultured AMs efficiently engraft in the lung and perform key macrophage functions.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Biology
Riem Gawish, Philipp Starkl, Lisabeth Pimenov, Anastasiya Hladik, Karin Lakovits, Felicitas Oberndorfer, Shane J. F. Cronin, Anna Ohradanova-Repic, Gerald Wirnsberger, Benedikt Agerer, Lukas Endler, Tumay Capraz, Jan W. Perthold, Domagoj Cikes, Rubina Koglgruber, Astrid Hagelkruys, Nuria Montserrat, Ali Mirazimi, Louis Boon, Hannes Stockinger, Andreas Bergthaler, Chris Oostenbrink, Josef M. Penninger, Sylvia Knapp
Summary: Despite progress in understanding COVID-19, limited mechanistic insight into immunological factors and disease severity remains. Scientists generated a mouse-adapted SARS-CoV-2 strain, maVie16, and found that cytokine-driven immunopathology and ACE2 dependence determine disease severity. This study provides a new tool for discovering therapies.
Article
Microbiology
Stefanie Widder, Irene Goerzer, Benjamin Friedel, Nina Rahimi, Stefan Schwarz, Peter Jaksch, Sylvia Knapp, Elisabeth Puchhammer-Stoeckl
Summary: This study provides a detailed analysis of virome dynamics after lung transplantation, revealing host, body compartment, and time-specific dependency patterns among viruses. The results also suggest genetic adaptation to the host microenvironment at the level of the virome and support the hypothesis of functional complementarity between Anellovirus groups and other persistent viruses.
Article
Multidisciplinary Sciences
Kevin Eislmayr, Annika Bestehorn, Luisa Morelli, Martina Borroni, Lieselotte Vande Walle, Mohamed Lamkanfi, Pavel Kovarik
Summary: IL-1α and IL-1β have distinct functions during infection, with IL-1α governing metabolic pathway reprogramming in the liver for infection tolerance, while IL-1β is essential for pathogen clearance and regulation of the spleen transcriptome.
Article
Medicine, Research & Experimental
Vanessa Monteil, Brett Eaton, Elena Postnikova, Michael Murphy, Benedict Braunsfeld, Ian Crozier, Franz Kricek, Janine Niederhofer, Alice Schwarzbock, Helene Breid, Stephanie Devignot, Jonas Klingstrom, Charlotte Thalin, Max J. Kellner, Wanda Christ, Sebastian Havervall, Stefan Mereiter, Sylvia Knapp, Anna Sanchez Jimenez, Agnes Bugajska-Schretter, Alexander Dohnal, Christine Ruf, Romana Gugenberger, Astrid Hagelkruys, Nuria Montserrat, Ivona Kozieradzki, Omar Hasan Ali, Johannes Stadlmann, Michael R. Holbrook, Connie Schmaljohn, Chris Oostenbrink, Robert H. Shoemaker, Ali Mirazimi, Gerald Wirnsberger, Josef M. Penninger
Summary: The emergence of multiple SARS-CoV-2 variants has raised concerns due to reduced vaccine efficacy and resistance to neutralizing antibody therapies. However, research shows that soluble ACE2 can inhibit current SARS-CoV-2 variants, providing proof of principle for a pan-SARS-CoV-2 therapeutic.
EMBO MOLECULAR MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Tim Hendrikx, Florentina Porsch, Mate G. Kiss, Dragana Rajcic, Nikolina Papac-Milicevic, Constanze Hoebinger, Laura Goederle, Anastasiya Hladik, Lisa E. Shaw, Hauke Horstmann, Sylvia Knapp, Sophia Derdak, Martin Bilban, Lena Heintz, Marcin Krawczyk, Rafael Paternostro, Michael Trauner, Matthias Farlik, Dennis Wolf, Christoph J. Binder
Summary: This study investigates the role of bone marrow-derived TREM2-expressing macrophages in non-alcoholic steatohepatitis (NASH). The results show that these macrophages are involved in hepatocellular damage, inflammation, and fibrosis in the liver. Soluble TREM2 levels in the blood are identified as a potential circulating marker for NASH.
JOURNAL OF HEPATOLOGY
(2022)
Article
Immunology
Sophie Zahalka, Philipp Starkl, Martin L. Watzenboeck, Asma Farhat, Mariem Radhouani, Florian Deckert, Anastasiya Hladik, Karin Lakovits, Felicitas Oberndorfer, Caroline Lassnig, Birgit Strobl, Kristaps Klavins, Mai Matsushita, David E. Sanin, Katarzyna M. Grzes, Edward J. Pearce, Anna-Dorothea Gorki, Sylvia Knapp
Summary: Environmental microbial exposure has a profound impact on pulmonary immune memory, particularly on alveolar macrophages (AMs). AMs showed enhanced reactivity to pneumococcal challenge after intranasal exposure to ambient lipopolysaccharide (LPS). The training effect of AMs was found to be dependent on type 1 interferon signaling and inhibited by fatty acid oxidation and glutaminolysis. Moreover, adoptive transfer of trained AMs resulted in increased bacterial loads and tissue damage upon pneumococcal infection.
MUCOSAL IMMUNOLOGY
(2022)
Editorial Material
Biotechnology & Applied Microbiology
Harald Hartweger, Michel C. Nussenzweig
Summary: Reprogramming of antibody responses in mice is achieved by delivering SaCas9, single guide RNA (sgRNA), and a repair template using adeno-associated virus.
NATURE BIOTECHNOLOGY
(2022)
Article
Biology
Riem Gawish, Barbara Maier, Georg Obermayer, Martin L. Watzenboeck, Anna-Dorothea Gorki, Federica Quattrone, Asma Farhat, Karin Lakovits, Anastasiya Hladik, Ana Korosec, Arman Alimohammadi, Ildiko Mesteri, Felicitas Oberndorfer, Fiona Oakley, John Brain, Louis Boon, Irene Lang, Christoph J. Binder, Sylvia Knapp
Summary: Sepsis can lead to multiorgan failure and therapeutic options are limited. This study establishes a mouse model of long-lasting disease tolerance during severe sepsis and highlights the role of neutrophils and B cells in tissue integrity.
Article
Immunology
Darryl A. Hayward, Lesley Vanes, Stefanie Wissmann, Sujana Sivapatham, Harald Hartweger, Joshua Biggs O'May, Leonard L. de Boer, Richard Mitter, Robert Kochl, Jens Stein, Victor L. J. Tybulewicz
Summary: In this study, the critical role of WNK1 kinase in regulating migration, adhesion, and activation of B cells was demonstrated. WNK1 transduces signals from BCR, CXCR5, and CD40, and controls the migration of naive and activated B cells as well as their interactions with T cells. Furthermore, WNK1 is necessary for BCR- and CD40-induced proliferation and efficient B cell-T cell collaboration in vivo.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Review
Oncology
Joshua Tobias, Mirjana Drinic, Anna Schmid, Anastasiya Hladik, Martin L. Watzenboeck, Claire Battin, Erika Garner-Spitzer, Peter Steinberger, Michael Kundi, Sylvia Knapp, Christoph C. Zielinski, Ursula Wiedermann
Summary: Therapies with monoclonal antibodies (mAbs) have revolutionized cancer treatment, but they have limitations such as frequent administration, limited clinical response duration, and immune-related adverse events. Vaccines using mimotopes that induce immunological memory and produce antibodies similar to mAbs have been proposed as an alternative. This review focuses on active immunization against two cancer-relevant targets and discusses safety concerns and future prospects.
Article
Biology
Sara Scinicariello, Adrian Soderholm, Markus Schaefer, Alexandra Shulkina, Irene Schwartz, Kathrin Hacker, Rebeca Gogova, Robert Kalis, Kimon Froussios, Valentina Budroni, Annika Bestehorn, Tim Clausen, Pavel Kovarik, Johannes Zuber, Gijs A. Versteeg
Summary: Tristetraprolin (TTP) stability is controlled by factors including lysine-ubiquitination and phosphorylation. The E3 ligase HUWE1 was identified as a regulator of TTP stability, indirectly controlling its phosphorylation. This study provides new insights into the regulation of TTP and its impact on immune response.
Article
Immunology
Harry B. Gristick, Harald Hartweger, Maximilian Loewe, Jelle van Schooten, Victor Ramos, Thiago Y. Oliveira, Yoshiaki Nishimura, Nicholas S. Koranda, Abigail Wall, Kai -Hui Yao, Daniel Poston, Anna Gazumyan, Marie Wiatr, Marcel Horning, Jennifer R. Keeffe, Magnus A. G. Hoffmann, Zhi Yang, Morgan E. Abernathy, Kim-Marie A. Dam, Han Gao, Priyanthi N. P. Gnanapragasam, Leesa M. Kakutani, Ana Jimena Pavlovitch-Bedzyk, Michael S. Seaman, Mark Howarth, Andrew T. Mcguire, Leonidas Stamatatos, Malcolm A. Martin, Anthony P. West Jr, Michel C. Nussenzweig, Pamela J. Bjorkman
Summary: Passive transfer of broadly neutralizing anti-HIV-1 antibodies is a strategy to protect against infection, but eliciting these antibodies through vaccination has been challenging. Researchers have successfully induced CD4 binding site (CD4bs) antibody responses using the antibody IOMA, which has potential as a vaccine strategy to generate broadly neutralizing antibodies against HIV-1.
SCIENCE IMMUNOLOGY
(2023)