Article
Immunology
Lukas Muri, Emma Ispasanie, Anna Schubart, Christine Thorburn, Natasa Zamurovic, Thomas Holbro, Michael Kammueller, Gerd Pluschke
Summary: Two different physiological opsonophagocytosis assay formats yielded consistent results, emphasizing the importance of alternative complement pathway activation for efficient killing in vaccine-naive individuals. In contrast, alternative pathway inhibition did not affect pneumococcal killing in PCV13-vaccinated subjects.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Yu Sun, Bin Xu, Xiangkai Zhuge, Fang Tang, Xuhang Wang, Qianwen Gong, Rui Chen, Feng Xue, Jianjun Dai
Summary: This study identified seven carbohydrate metabolic enzymes (CMEs) located on the outer membrane of ExPEC, which recruit Factor H (FH) and enhance its resistance to complement-mediated killing, providing insights into the pathogenic mechanism of ExPEC.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Carolin Schmidt, Sabrina Weissmueller, Fabian Bohlaender, Matthias Germer, Martin Koenig, Alexander Staus, Andrea Wartenberg-Demand, Corina C. Heinz, Joerg Schuettrumpf
Summary: The study shows that Trimodulin treatment can activate the complement system, enhance opsonophagocytosis, and interact with C3b, C4b, and C5a in a concentration-dependent manner. In patients with severe infections, Trimodulin can prevent excessive pathogen lysis and harmful C5a release.
Article
Immunology
Lukas Muri, Anna Schubart, Christine Thorburn, Natasa Zamurovic, Thomas Holbro, Michael Kammueller, Gerd Pluschke, Emma Ispasanie
Summary: Defense against Haemophilus influenzae type b (Hib) depends on antibodies and complement, which can mediate both serum bactericidal activity (SBA) and opsonophagocytosis. Inhibitors targeting complement factors C3 or C5 may be used as alternative treatment options, with a potentially improved safety profile of AP inhibitors over C3 and C5 inhibitors. Vaccination can mitigate the inhibitory effect of AP inhibition on SBA.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Public, Environmental & Occupational Health
Rola Husni, Maroun Bou Zerdan, Nadia Samaha, Mariana Helou, Youssef Mahfouz, Rim Saniour, Sawsan Hourani, Harout Kolanjian, Claude Afif, Eid Azar, Tamima El Jisr, Jacques Mokhbat, Emma Abboud, Rita Feghali, Edmond Abboud, Hiam Matta, Gilbert Karayakouboglo, Madonna Matar, Rima Moghnieh, Ziad Daoud
Summary: This study describes the epidemiology of non-albicans Candida (NAC) infections and their resistance in Lebanese hospitals. The most common NAC species isolated were Candida glabrata (40.8%) and Candida tropicalis (23.1%). The study also found differing susceptibility to antifungal treatments among these species. Proper identification of these organisms is crucial for effective treatment.
FRONTIERS IN PUBLIC HEALTH
(2023)
Article
Microbiology
Juan David Ramirez, Chin Yi Wang, Deandra Bolton, Bernadette Liggayu, Sarah Schaefer, Gopi Patel, Waleed Javaid, Carlos Cordon-Cardo, Adolfo Firpo-Betancourt, Emilia Mia Sordillo, Alberto Paniz-Mondolfi
Summary: This study validates the DiaSorin Molecular C.auris Detection Kit for accurate and rapid detection of C. auris. The assay shows high sensitivity and specificity, and can aid in timely implementation of infection control measures and appropriate patient care.
Article
Biochemistry & Molecular Biology
Yi Liu, Zhao Lv, Tiaoyi Xiao, Xuewen Zhang, Chunhua Ding, Beibei Qin, Baohong Xu, Qiaolin Liu
Summary: The study demonstrates the important role of complement factor I (CFI) in regulating the complement system and host defense against pathogens in grass carp. Cloning and functional analysis of the CiCFI gene reveal its involvement in degrading serum C3b and its expression regulation after GCRV infection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Sosuke Fukui, Masashi Mizuno, Mitsuhiro Tawada, Yasuhiro Suzuki, Hiroshi Kojima, Yoshihisa Matsukawa, Masaki Imai, Hangsoo Kim, Hiroshi Kinashi, Makoto Mizutani, Kenichi Minoshima, Shoichi Maruyama, Yasuhiko Ito
Summary: This study investigated the expression of membrane complement regulators and tissue injuries in peritoneal dialysis-related peritonitis. The results showed that peritonitis led to severe peritoneal injuries and decreased expression of membrane complement regulators. Fungal and Pseudomonas aeruginosa peritonitis were associated with more severe injuries compared to Gram-positive bacterial peritonitis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Xinhai Chen, Haley Gula, Tonu Pius, Chong Ou, Margaryta Gomozkova, Lai-Xi Wang, Olaf Schneewind, Dominique Missiakas
Summary: This study reveals that the clearance of Staphylococcus aureus is achieved through different mechanisms mediated by different subclasses of antibodies. FcγRIV is the main protective pathway for antibody 3F6-mIgG2a in C57BL/6J mice, while CR3 serves as the main pathway in BALB/cJ mice. These findings may have clinical implications in predicting the efficacy of antibody therapies and could be relevant in other mammals including humans.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Multidisciplinary
Lan Lin, Moran Wang, Jingsi Zeng, Yehong Mao, Renjie Qin, Jun Deng, Xiaohu Ouyang, Xiaoshuang Hou, Chunyan Sun, Yadan Wang, Yaohua Cai, Mingyue Li, Chunxia Tian, Xi Zhou, Min Zhang, Heng Fan, Heng Mei, Alexey Sarapultsev, Huafang Wang, Gensheng Zhang, Peter F. Zipfel, Yu Hu, Desheng Hu, Shanshan Luo
Summary: This study investigates the systemic immune responses triggered by C. albicans and identifies novel evasion strategies used by clinical isolates. A disease-associated variation of Sap2 at nucleotide position 817 is identified, which enhances pathogenicity. In mice infected with the Sap2-273L strain, there is less complement activation, increased degradation of C3 and C3b, and a shift towards a M2-like macrophage phenotype and immunosuppressed cellular microenvironment characterized by more Tregs and exhausted T cells.
Article
Immunology
Meng Wu, Bei-bei Jia, Mo-fei Li
Summary: This study investigated the immunological properties of C3 and C3a in Japanese flounder and found that PoC3 is expressed in nine different tissues and upregulated by bacterial challenge. PoC3 in serum can bind to a broad-spectrum of bacteria and directly kill specific pathogens. Knocking down PoC3 expression significantly decreases complement activity and increases bacterial replication in fish tissues. Recombinant PoC3a exhibits binding capacities to bacteria and immune cells, and administration of rPoC3a enhances resistance against bacterial infection.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Noriko Shinjyo, Kenji Hikosaka, Yasutoshi Kido, Hiroki Yoshida, Kazumi Norose
Summary: The study investigated the impact of Toxoplasma infection on mRNA levels of complement components, revealing significant upregulation of multiple components at 2 weeks and 2 months post-infection, as well as changes in mixed glial cell culture. These findings shed new light on the role of the complement system in the brain parenchyma during Toxoplasma infection, potentially leading to the development of novel therapeutic approaches for Toxoplasma infection-induced neurological disorders.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Paula Niewold, Douwe J. Dijkstra, Yi Cai, Delia Goletti, Fabrizio Palmieri, Krista E. van Meijgaarden, Frank A. W. Verreck, Onno W. Akkerman, Regina W. Hofland, Eveline M. Delemarre, Stefan Nierkens, Marije K. Verheul, Andrew J. Pollard, Jaap T. van Dissel, Tom H. M. Ottenhoff, Leendert A. Trouw, Simone A. Joosten
Summary: Tuberculosis (TB) is a common disease with high mortality and morbidity rates. Differentiating TB from other diseases is challenging, especially in clinical settings. The study identified circulating monocytes as the source of complement component C1q, which is a specific biomarker for TB. The expression of C1q was pronounced in classical and intermediate monocytes and varied in non-classical monocytes.
SCIENTIFIC REPORTS
(2023)
Article
Medicine, General & Internal
Christos Koutserimpas, Symeon Naoum, Kalliopi Alpantaki, Konstantinos Raptis, Konstantinos Dretakis, Georgia Vrioni, George Samonis
Summary: Fungal prosthetic joint infections (PJIs), especially in revised knee arthroplasties, are rare but devastating complications. This article reports a case of Candida parapsilosis PJI and provides a review of published fungal PJIs in revised knee arthroplasties. The combination of antifungal treatment and two-stage revision arthroplasty seems to be the preferred treatment, with a success rate of 82.6%.
Article
Microbiology
Fatima Allaw, Nada Kara Zahreddine, Ahmad Ibrahim, Joseph Tannous, Hussein Taleb, Abdul Rahman Bizri, Ghassan Dbaibo, Souha S. Kanj
Summary: This study reported the first cases of Candida auris infection in Lebanon, focusing on clinical features, infection control investigation and interventions. A total of 14 patients with C. auris infection/colonization were identified using MALDI-TOF and VITEK 2-Compact system. Half of the patients were infected with COVID-19 prior to C. auris isolation, highlighting the importance of rapid case detection and reporting to prevent further hospital transmission.
Article
Biochemistry & Molecular Biology
Yaseelan Palarasah, Anne Sofie L. ogstrup Henriksen, Steffen Thiel, Maiken Henriksen, Soren W. K. Hansen
Summary: The serine protease MASP-3 mediates the conversion of pro-factor D to mature factor D in the complement system. This discovery suggests that pattern recognition of pathogen/danger-associated molecular patterns may be a prior requirement for all complement activation.
MOLECULAR IMMUNOLOGY
(2022)
Article
Gastroenterology & Hepatology
Tea Lund Laursen, Lars Bossen, Rasmus Pihl, Anne Troldborg, Thomas Damgaard Sandahl, Annette Gudmann Hansen, Trine Folserass, Mette Vesterhus, Henning Gronbaek, Steffen Thiel
Summary: The study found significantly elevated plasma concentrations of ITIH4 in patients with PBC and PSC compared to the healthy control group. ITIH4 may be a potential biomarker for cholestatic liver diseases.
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
(2022)
Article
Immunology
Jens Magnus Bernth Jensen, Anette Tarp Hansen, Anna Soderstorm, Charlotte Svaerke Jorgensen, Carsten Schade Larsen, Uffe B. Skov Sorensen, Steffen Thiel, Mikkel Steen Petersen
Summary: This study aimed to investigate whether the levels of naturally occurring antibodies against alpha Gal can serve as alternative markers of functional antibody capacity. The study included data from 229 patients with suspected primary immunodeficiency in a retrospective study. The results showed a positive correlation between anti-alpha Gal antibody levels and anti-pneumococcal antibody levels, and the former showed potential for predicting subsequent immunoglobulin treatment.
CLINICAL IMMUNOLOGY
(2022)
Article
Biochemical Research Methods
Maiken Lumby Henriksen, Christian Nielsen, Dennis Pedersen, Gregers Rom Andersen, Steffen Thiel, Yaseelan Palarasah, Soren Werner Karlskov Hansen
Summary: Factor D is a serine protease involved in immune responses and antibody functions. The mature form of factor D is the most abundant in circulation, while the pro-form accounts for 8-15% of total factor D. Blood sampling procedures can affect conversion and measurement levels.
JOURNAL OF IMMUNOLOGICAL METHODS
(2022)
Article
Immunology
Clara Elbaek Mistegaard, Lisbeth Jensen, Mette Christiansen, Mette Bjerre, Jens Magnus Bernth Jensen, Steffen Thiel
Summary: CVID patients have lower levels of complement proteins compared to healthy individuals, suggesting a potential role of the complement system in the development of CVID.
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Henrik Pedersen, Rasmus Kjeldsen Jensen, Annette Gudmann Hansen, Steen Vang Petersen, Steffen Thiel, Nick Stub Laursen, Gregers Rom Andersen
Summary: The complement system plays a role in labeling pathogens and dying host cells for clearance. A nanobody has been discovered that specifically binds to degradation products of complement component C3 and effectively inhibits complement deposition. This nanobody could be a potential candidate for studying complement-related diseases in rodent models.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Vivien R. Schack, Morten K. Herlin, Henrik Pedersen, J. Magnus Bernth Jensen, Mia Faerch, Bettina Bundgaard, Rasmus K. Jensen, Uffe B. Jensen, Rikke Christensen, Gregers R. Andersen, Steffen Thiel, Per Hollsberg
Summary: We report a pediatric patient with aHUS carrying a previously unreported homozygous variant in CD46. Functional analyses showed that this variant caused complement dysregulation through multiple mechanisms. These findings highlight the coexistence of multiple mechanisms that may disrupt CD46 function during aHUS development.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Microbiology
Nadia Sitoe, Mohamed Ahmed, Maria Enosse, Abhishek Bakuli, Raquel Chissumba, Kathrin Held, Michael Hoelscher, Pedroso Nhassengo, Celso Khosa, Andrea Rachow, Christof Geldmacher
Summary: HIV infection leads to immune activation and affects the progression of tuberculosis. This study found that activation markers on MTB-specific CD4+ T-cells decreased after anti-tuberculosis treatment initiation, regardless of HIV status and lung impairment severity. The expression of the maturation marker, CD27, did not change during TB treatment. Evaluating the activation and maturation markers on MTB-specific CD4+ T-cells can be useful for monitoring TB treatment, regardless of HIV status and the severity of lung disease.
Article
Hematology
Julie Brogaard Larsen, Rasmus Pihl, Mathies Appel Aggerbeck, Kim Michael Larsen, Christine Lodberg Hvas, Nanna Johnsen, Mette G. Christensen, Helle Praetorius, Anne-Mette Hvas, Steffen Thiel
Summary: The study investigates the association between ITIH4 levels and sepsis-related coagulopathy, indicating that ITIH4 is not an acute-phase reactant during septic shock.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Allergy
Laura Barrett Ryo, Didde Haslund, Anne Bruun Rovsing, Rasmus Pihl, Wariya Sanrattana, Steven de Maat, Yaseelan Palarasah, Coen Maas, Steffen Thiel, Jacob Giehm Mikkelsen
Summary: This study investigates the trans-inhibitory effects of different SERPING1 variants on the expression, secretion, functionality, and intracellular localization of C1 inhibitor (C1INH) in HeLa cells. The findings suggest that different SERPING1 variants may drive the pathogenicity of hereditary angioedema through different and sometimes overlapping molecular disease mechanisms, with some variants acting as dominant-negative factors.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Alexey Ferapontov, Marjan Omer, Isabelle Baudrexel, Jesper Sejrup Nielsen, Daniel Miotto Dupont, Kristian Juul-Madsen, Philipp Steen, Alexandra S. Eklund, Steffen Thiel, Thomas Vorup-Jensen, Ralf Jungmann, Jorgen Kjems, Soren Egedal Degn
Summary: The binding between B cell receptors (BCRs) and antigens triggers a response in B cells and eventually leads to antibody production. However, it is still unclear how BCRs are distributed on naive B cells and how antigen binding initiates the first step of BCR signaling. Using DNA-PAINT super-resolution microscopy, it has been discovered that most BCRs exist as monomers, dimers, or loosely associated clusters on resting B cells, with a nearest-neighbor inter-Fab distance of 20-30nm. By engineering monoclonal model antigens with precise control over affinity and valency, researchers found that the antigen can activate the BCR in an agonistic manner as affinity and avidity increase.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Tabea M. Eser, Olga Baranov, Manuel Huth, Mohammed I. M. Ahmed, Flora Deak, Kathrin Held, Luming Lin, Kami Pekayvaz, Alexander Leunig, Leo Nicolai, Georgios Pollakis, Marcus Buggert, David A. Price, Raquel Rubio-Acero, Jakob Reich, Philine Falk, Alissa Markgraf, Kerstin Puchinger, Noemi Castelletti, Laura Olbrich, Kanika Vanshylla, Florian Klein, Andreas Wieser, Jan Hasenauer, Inge Kroidl, Michael Hoelscher, Christof Geldmacher
Summary: The study shows that systemic inflammation markers are directly correlated with upper airways viral loads, while the frequencies of nucleocapsid-specific CD4(+) and CD8(+) T cells are inversely correlated with inflammatory markers and viral loads. The presence of activated T cells expressing cytotoxic proteins and IFN-gamma in infected epithelium is linked with better control of SARS-CoV-2. These findings provide insights for the development of vaccines against COVID-19.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Mads Lamm Larsen, Anne Troldborg, Erik J. M. Toonen, Lisa Hurler, Zoltan Prohaszka, Laszlo Cervenak, Annette Gudmann Hansen, Steffen Thiel
Summary: This study aims to differentiate between classical or lectin pathway-mediated complement activation in SLE patients by quantifying pathway-specific protein complexes. The classical pathway is activated in active SLE disease, whereas activation of the lectin pathway might be more specific to disease manifestations like lupus nephritis.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Moritz Lasse, Jamal El Saghir, Celine C. Berthier, Sean Eddy, Matthew Fischer, Sandra D. Laufer, Dominik Kylies, Arvid Hutzfeldt, Lena Lydie Bonin, Bernhard Dumoulin, Rajasree Menon, Virginia Vega-Warner, Felix Eichinger, Fadhl Alakwaa, Damian Fermin, Anja M. Billing, Akihiro Minakawa, Phillip J. McCown, Michael P. Rose, Bradley Godfrey, Elisabeth Meister, Thorsten Wiech, Mercedes Noriega, Maria Chrysopoulou, Paul Brandts, Wenjun Ju, Linda Reinhard, Elion Hoxha, Florian Grahammer, Maja T. Lindenmeyer, Tobias B. Huber, Hartmut Schlueter, Steffen Thiel, Laura H. Mariani, Victor G. Puelles, Fabian Braun, Matthias Kretzler, Fatih Demir, Jennifer L. Harder, Markus M. Rinschen
Summary: Kidney organoids are a promising model for studying kidney disease. By analyzing the proteome and transcriptome of the organoids, researchers found that older organoids deposit more extracellular matrix and express fewer glomerular proteins. Treatment with TNF-α resulted in differential expression of 322 proteins, including cytokines and complement components. Integration of transcriptomic data revealed that these proteins were associated with poorer clinical outcomes in proteinuric kidney disease patients. This study demonstrates the functional relevance of kidney organoids in modeling human kidney disease.
NATURE COMMUNICATIONS
(2023)
Article
Gastroenterology & Hepatology
Tea Lund Laursen, Lars Bossen, Rasmus Pihl, Anne Troldborg, Thomas Damgaard Sandahl, Annette Gudmann Hansen, Trine Folserass, Mette Vesterhus, Henning Gronbaek, Steffen Thiel
Summary: The plasma concentration of ITIH4 was significantly elevated in patients with PBC and PSC, with correlations observed with IgM levels and lower concentrations in responders to UDCA treatment. Increased ITIH4 staining was seen in immunohistochemistry, indicating its potential role as a biomarker in cholestatic liver diseases.
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
(2022)
