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Journal Front Immunol

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Increased Prevalence of NLRP3 Q703K Variant Among Patients With Autoinflammatory Diseases: An International Multicentric Study.

Katerina Theodoropoulou, Helmut Wittkowski, Nathalie Busso, Annette Von Scheven-Gête, Isabelle Moix, Federica Vanoni, Veronique Hengten, Gerd Horneff, Johannes-Peter Haas, Nadine Fischer, Katharina Palm-Beden, Rainer Berendes, Georg Heubner, Annette Jansson, Elke Lainka, Annette Leimgruber, Michael Morris, Dirk Foell, Michaël Hofer,

Background: The NLRP3 inflammasome has been recognized as one of the key components of innate immunity. Gain-of-function mutations in the exon 3 of NLRP3 gene have been implicated in inflammatory diseases suggesting the presence of functionally important sites in this region. Q703K (c.2107C>A, p.Gln703Lys, also known in the literature as ... Read more >>

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Immunogenicity of Protein Therapeutics: A Lymph Node Perspective.

Kristy Fu, Kylie March, Aikaterini Alexaki, Giulia Fabozzi, Eirini Moysi, Constantinos Petrovas,

The continuous development of molecular biology and protein engineering technologies enables the expansion of the breadth and complexity of protein therapeutics for in vivo administration. However, the immunogenicity and associated in vivo development of antibodies against therapeutics are a major restriction factor for their usage. The B cell follicular and ... Read more >>

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Maternal Latent Mycobacterium tuberculosis Does Not Affect the Infant Immune Response Following BCG at Birth: An Observational Longitudinal Study in Uganda.

Lawrence Lubyayi, Patrice A. Mawa, Grace Nabakooza, Marjorie Nakibuule, John Vianney Tushabe, Joel Serubanja, Dorothy Aibo, Hellen Akurut, Josephine Tumusiime, Mateusz Hasso-Agopsowicz, Pontiano Kaleebu, Jonathan Levin, Hazel M. Dockrell, Steven Smith, Emily L. Webb, Alison M. Elliott, Stephen Cose,

Background: BCG has low efficacy in tropical countries. We hypothesized that maternal latent Mycobacterium tuberculosis (M.tb) infection (LTBI) results in fetal tolerance to mycobacterial antigens and impaired responses to BCG immunization.Methods: We enrolled 132 LTBI-positive and 150 LTBI-negative mothers and their babies in Entebbe, Uganda. Infants were BCG-immunized at birth. ... Read more >>

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Relevance of the Materno-Fetal Interface for the Induction of Antigen-Specific Immune Tolerance.

Angelina Mimoun, Sandrine Delignat, Ivan Peyron, Victoria Daventure, Maxime Lecerf, Jordan D. Dimitrov, Srinivas V. Kaveri, Jagadeesh Bayry, Sébastien Lacroix-Desmazes,

In humans, maternal IgGs are transferred to the fetus from the second trimester of pregnancy onwards. The transplacental delivery of maternal IgG is mediated by its binding to the neonatal Fc receptor (FcRn) after endocytosis by the syncytiotrophoblast. IgGs present in the maternal milk are also transferred to the newborn ... Read more >>

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Immunoglobulin G Subclass-Specific Glycosylation Changes in Primary Epithelial Ovarian Cancer.

Marta Wieczorek, Elena Ioana Braicu, Leticia Oliveira-Ferrer, Jahid Sehouli, Véronique Blanchard,

Epithelial ovarian cancer (EOC) was previously shown to be associated with glycosylation changes of total serum and total IgG proteins. However, as a majority of previous studies analyzed released glycan profiles, still little is known about IgG subclass-specific alterations in ovarian cancer. Hence, in this study, we investigated EOC-related glycosylation ... Read more >>

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Brain Ischemia Significantly Alters microRNA Expression in Human Peripheral Blood Natural Killer Cells.

Ying Kong, Shiyao Li, Xiaojing Cheng, Honglei Ren, Bohao Zhang, Hongshan Ma, Minshu Li, Xiao-An Zhang,

Brain ischemia induces systemic immunosuppression and increases a host's susceptibility to infection. MicroRNAs (miRNAs) are molecular switches in immune cells, but the alterations of miRNAs in human immune cells in response to brain ischemia and their impact on immune defense remain elusive. Natural killer (NK) cells are critical for early ... Read more >>

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A Functional Genetic Variant at the C-Reactive Protein Promoter (rs3091244) Is Not Associated With Cancer Risk in a Chinese Population.

Ming-Yu Wang, Hai-Hong Zhou, Chun-Miao Zhang, Hai-Xiang Su, Shuo-Lei Li, Shang-Rong Ji, Enqi Liu, Yi Wu,

Background: The association of genetically elevated levels of circulating C-reactive protein (CRP) with cancer risk has been extensively investigated in European populations; however, there are conflicting conclusions. The tri-allelic rs3091244 is a functionally validated genetic variant, and its allelic frequencies differ significantly between European and Asian populations. Here, we examined ... Read more >>

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Serum Amyloid A1 (SAA1) Revisited: Restricted Leukocyte-Activating Properties of Homogeneous SAA1.

Sara Abouelasrar Salama, Mirre De Bondt, Mieke De Buck, Nele Berghmans, Paul Proost, Vivian Louise Soares Oliveira, Flavio A. Amaral, Mieke Gouwy, Jo Van Damme, Sofie Struyf,

Infection, sterile injury, and chronic inflammation trigger the acute phase response in order to re-establish homeostasis. This response includes production of positive acute phase proteins in the liver, such as members of the serum amyloid A (SAA) family. In humans the major acute phase SAAs comprise a group of closely ... Read more >>

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Editorial: Understanding Gamma Delta T Cell Multifunctionality - Towards Immunotherapeutic Applications.

Kenth Gustafsson, Thomas Herrmann, Francesco Dieli,

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Inhibitory Effects of Dietary N-Glycans From Bovine Lactoferrin on Toll-Like Receptor 8; Comparing Efficacy With Chloroquine.

Susana Figueroa-Lozano, Rivca L. Valk-Weeber, Renate Akkerman, Wayel Abdulahad, Sander S. van Leeuwen, Lubbert Dijkhuizen, Paul de Vos,

Toll-like receptor 8 (TLR-8) plays a role in the pathogenesis of autoimmune disorders and associated gastrointestinal symptoms that reduce quality of life of patients. Dietary interventions are becoming more accepted as mean to manage onset, progression, and treatment of a broad spectrum of inflammatory conditions. In this study, we assessed ... Read more >>

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Global Repertoire of Human Antibodies Against Plasmodium falciparum RIFINs, SURFINs, and STEVORs in a Malaria Exposed Population.

Bernard N. Kanoi, Hikaru Nagaoka, Michael T. White, Masayuki Morita, Nirianne M. Q. Palacpac, Edward H. Ntege, Betty Balikagala, Adoke Yeka, Thomas G. Egwang, Toshihiro Horii, Takafumi Tsuboi, Eizo Takashima,

Clinical immunity to malaria develops after repeated exposure to Plasmodium falciparum parasites. Broadly reactive antibodies against parasite antigens expressed on the surface of infected erythrocytes (variable surface antigens; VSAs) are candidates for anti-malaria therapeutics and vaccines. Among the VSAs, several RIFIN, STEVOR, and SURFIN family members have been demonstrated to ... Read more >>

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Mycobacterium tuberculosis Infection-Driven Foamy Macrophages and Their Implications in Tuberculosis Control as Targets for Host-Directed Therapy.

Dahee Shim, Hagyu Kim, Sung Jae Shin,

Tuberculosis (TB) is a leading cause of death worldwide following infection with Mycobacterium tuberculosis (Mtb), with 1.5 million deaths from this disease reported in 2018. Once the bacilli are inhaled, alveolar and interstitial macrophages become infected with Mtb and differentiate into lipid-laden foamy macrophages leading to lung inflammation. Thus, the ... Read more >>

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Leukocyte Immunoglobulin-Like Receptors (LILRs) on Human Neutrophils: Modulators of Infection and Immunity.

Alexander L. Lewis Marffy, Alex J. McCarthy,

Neutrophils have a crucial role in defense against microbes. Immune receptors allow neutrophils to sense their environment, with many receptors functioning to recognize signs of infection and to promote antimicrobial effector functions. However, the neutrophil response must be tightly regulated to prevent excessive inflammation and tissue damage, and regulation is ... Read more >>

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Tolerizing Strategies for the Treatment of Autoimmune Diseases: From ex vivo to in vivo Strategies.

Anje Cauwels, Jan Tavernier,

Autoimmune diseases such as multiple sclerosis (MS), type I diabetes (T1D), inflammatory bowel diseases (IBD), and rheumatoid arthritis (RA) are chronic, incurable, incapacitating and at times even lethal conditions. Worldwide, millions of people are affected, predominantly women, and their number is steadily increasing. Currently, autoimmune patients require lifelong immunosuppressive therapy, ... Read more >>

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Altered Gut Microbiota and Immunity Defines Plasmodium vivax Survival in Anopheles stephensi.

Punita Sharma, Jyoti Rani, Charu Chauhan, Seena Kumari, Sanjay Tevatiya, Tanwee Das De, Deepali Savargaonkar, Kailash C. Pandey, Rajnikant Dixit,

Blood-feeding enriched gut-microbiota boosts mosquitoes' anti-Plasmodium immunity. Here, we ask how Plasmodium vivax alters gut-microbiota, anti-Plasmodial immunity, and impacts tripartite Plasmodium-mosquito-microbiota interactions in the gut lumen. We used a metagenomics and RNAseq strategy to address these questions. In naïve mosquitoes, Elizabethkingia meningitis and Pseudomonas spp. are the dominant bacteria and ... Read more >>

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A Pro- and Anti-inflammatory Axis Modulates the Macrophage Circadian Clock.

Shan Chen, Kevin K. Fuller, Jay C. Dunlap, Jennifer J. Loros,

The circadian clock broadly governs immune cell function, leading to time-of-day differences in inflammatory responses and subsequently, pathogen clearance. However, the effect of inflammatory signals on circadian machinery is poorly understood. We found that in bone marrow-derived macrophages, some host-derived pro-inflammatory cytokines, e.g., IFN-γ or TNF-α, and pathogen-associated molecular patterns, ... Read more >>

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Characterization of the Porcine CLEC12A and Analysis of Its Expression on Blood Dendritic Cell Subsets.

Belén Álvarez, Elvira Nieto-Pelegrín, Paloma Martínez de la Riva, Daisuke Toki, Teresa Poderoso, Concepción Revilla, Hirohide Uenishi, Angel Ezquerra, Javier Domínguez,

CLEC12A has been proposed as a suitable target for delivering antigen to dendritic cells (DCs) to enhance vaccine efficacy both in human and mouse. In this study, we have characterized the porcine homolog of CLEC12A (poCLEC12A). Using new monoclonal antibodies (mAb), raised against its ectodomain, poCLEC12A was found to be ... Read more >>

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Desferrioxamine Supports Metabolic Function in Primary Human Macrophages Infected With Mycobacterium tuberculosis.

James Joseph Phelan, Kate McQuaid, Colin Kenny, Karl Michael Gogan, Dónal J. Cox, Sharee Ann Basdeo, Seónadh O’Leary, Simone Christa Tazoll, Cilian Ó Maoldomhnaigh, Mary P. O’Sullivan, Luke A. O’Neill, Maureen J. O’Sullivan, Joseph Keane,

Tuberculosis is the single biggest infectious killer in the world and presents a major global health challenge. Antimicrobial therapy requires many months of multiple drugs and incidences of drug resistant tuberculosis continues to rise. Consequently, research is now focused on the development of therapies to support the function of infected ... Read more >>

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Mesothelioma in Familial Mediterranean Fever With Colchicine Intolerance: A Case Report and Literature Review.

Rosa Talerico, Carmine Cardillo, Francesco De Vito, Francesca Schinzari, Manuel Soldato, Maria Cristina Giustiniani, Elena Verrecchia, Raffaele Manna,

A 65-year-old Italian physician affected by Familial Mediterranean fever (FMF) was hospitalized due to progressive abdominal enlargement, which had begun 6 months before admission. Physical examination revealed ascites and bilateral leg edema. Abdominal CT scan showed ascitic fluid and extensive multiple peritoneal implants; peritoneal CT-guided biopsy revealed an epithelial-type malignant ... Read more >>

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Transcriptional Regulation of Osteoclastogenesis: The Emerging Role of KLF2.

Daniela Rolph, Hiranmoy Das,

Dysregulation of osteoclastic differentiation and its activity is a hallmark of various musculoskeletal disease states. In this review, the complex molecular factors underlying osteoclastic differentiation and function are evaluated. The emerging role of KLF2 in regulation of osteoclastic differentiation is examined, specifically in the context of rheumatoid arthritis in which ... Read more >>

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Treated HIV Infection Alters Phenotype but Not HIV-Specific Function of Peripheral Blood Natural Killer Cells.

Nancy Q. Zhao, Anne-Maud Ferreira, Philip M. Grant, Susan Holmes, Catherine A. Blish,

Natural killer (NK) cells are the predominant antiviral cells of the innate immune system, and may play an important role in acquisition and disease progression of HIV. While untreated HIV infection is associated with distinct alterations in the peripheral blood NK cell repertoire, less is known about how NK phenotype ... Read more >>

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CASK, the Soluble Glomerular Permeability Factor, Is Secreted by Macrophages in Patients With Recurrent Focal and Segmental Glomerulo—Sclerosis.

Xiaomeng Zhang, Florence Herr, Amelia Vernochet, Hans K. Lorenzo, Séverine Beaudreuil, Antoine Dürrbach,

Introduction: Focal and segmental glomerulosclerosis (FSGS) is a frequent form of glomerulonephritis that may be caused by a soluble permeability factor and regulated by the immune system. We previously described a soluble form of calcium/calmodulin-dependent serine/threonine kinase (CASK) acting as a permeability factor in patients with recurrent FSGS (rFSGS). Here, ... Read more >>

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GDF15 Plasma Level Is Inversely Associated With Level of Physical Activity and Correlates With Markers of Inflammation and Muscle Weakness.

Maria Conte, Morena Martucci, Giovanni Mosconi, Antonio Chiariello, Maria Cappuccilli, Valentina Totti, Aurelia Santoro, Claudio Franceschi, Stefano Salvioli,

Growth differentiation factor 15 (GDF15) is a stress molecule produced in response to mitochondrial, metabolic and inflammatory stress with a number of beneficial effects on metabolism. However, at the level of skeletal muscle it is still unclear whether GDF15 is beneficial or detrimental. The aim of the study was to ... Read more >>

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Implications of COVID-19 Outbreak on Immune Therapies in Multiple Sclerosis Patients—Lessons Learned From SARS and MERS.

Nora Möhn, Refik Pul, Christoph Kleinschnitz, Harald Prüss, Torsten Witte, Martin Stangel, Thomas Skripuletz,

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic keeps the world in suspense. In addition to the fundamental challenges for the health care system, the individual departments must decide how to deal with patients at risk. Neurologists are confronted with the question, how they should advise their patients regarding immunosuppressive treatment. ... Read more >>

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Adaptive Immunity Regulation and Cerebral Ischemia.

Xingping Qin, Farhana Akter, Lingxia Qin, Jing Cheng, Mei Guo, Shun Yao, Zhihong Jian, Renzhong Liu, Songlin Wu,

Stroke is a disease that occurs due to a sudden interruption of the blood supply to the brain. It is a leading cause of death and disability worldwide. It is well-known that the immune system drives brain injury following an episode of ischemic stroke. The innate system and the adaptive ... Read more >>

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