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Transitional b cell infection

Rajakumar Mandraju, Aakanksha Jain, Yajing Gao, Zhiming Ouyang, Michael V Norgard, Chandrashekhar Pasare
Activation of CD4 T cells by dendritic cells leads to their differentiation into various effector lineages. The nature of the effector lineage is determined by the innate cues provided by dendritic cells to newly primed T cells. Although the cytokines necessary for several effector lineages have been identified, the innate cues that drive Tfh lineage development remain unclear. Here we find that following priming, CD4 T cells undergoing clonal expansion acquire a transient Tfh-like phenotype before differentiating into other effector lineages...
March 5, 2018: Infection and Immunity
Elena Blanco, Martín Pérez-Andrés, Sonia Arriba-Méndez, Teresa Contreras-Sanfeliciano, Ignacio Criado, Ondrej Pelak, Ana Serra-Caetano, Alfonso Romero, Noemí Puig, Ana Remesal, Juan Torres Canizales, Eduardo López-Granados, Tomas Kalina, Ana E Sousa, Menno Van Zelm, Mirjam Van der Burg, Jacques J M van Dongen, Alberto Orfao
BACKGROUND: Humoral immunocompetence develops stepwise throughout life and contributes to individual susceptibility to infection, immunodeficiency, autoimmunity and neoplasia. Immunoglobulin heavy chain (IgH)-isotype serum levels can partly explain such age-related differences, but their relationship with the IgH-isotype distribution within memory B-cell (MBCs) and plasma cell (PCs) compartments remains to be investigated. OBJECTIVE: We studied the age-related distribution of MBCs and PCs expressing different IgH-isotypes, in addition to the immature/transitional and naive B-cell compartments...
March 2, 2018: Journal of Allergy and Clinical Immunology
Sawsan Sudqi Said, Guliz Tuba Barut, Nesteren Mansur, Asli Korkmaz, Ayca Sayi-Yazgan
Regulatory B cells (Bregs) play a crucial role in immunological tolerance primarily through the production of IL-10 in many diseases including autoimmune disorders, allergy, infectious diseases, and cancer. To date, various Breg subsets with overlapping phenotypes have been identified. However, the roles of Bregs in Helicobacter infection are largely unknown. In the present study, we investigate the phenotype and function of Helicobacter -stimulated B cells. Our results demonstrate that Helicobacter felis -stimulated IL-10- producing B cells (Hfstim - IL-10+ B) are composed of B10 and Transitional 2 Marginal Zone Precursor (T2-MZP) cells with expression of CD9, Tim-1, and programmed death 1 (PD-1)...
February 26, 2018: Molecular Immunology
Howard A Burris, Ian W Flinn, Manish R Patel, Timothy S Fenske, Changchun Deng, Danielle M Brander, Martin Gutierrez, James H Essell, John G Kuhn, Hari P Miskin, Peter Sportelli, Michael S Weiss, Swaroop Vakkalanka, Michael R Savona, Owen A O'Connor
BACKGROUND: Umbralisib (TGR-1202) is a novel next-generation inhibitor of phosphatidylinositol 3-kinase (PI3K) isoform p110δ (PI3Kδ), which is structurally distinct from other PI3Kδ inhibitors and shows improved isoform selectivity. Umbralisib also uniquely inhibits casein kinase-1ε, a major regulator of protein translation. The aim of this first-in-human phase 1 study was to establish the safety and preliminary activity profile of umbralisib in patients with haematological malignancies...
February 20, 2018: Lancet Oncology
Madeleine E Zinser, Andrew J Highton, Ayako Kurioka, Barbara Kronsteiner, Joachim Hagel, Tianqi Leng, Emanuele Marchi, Chansavath Phetsouphanh, Chris B Willberg, Susanna J Dunachie, Paul Klenerman
Mucosal-associated invariant T (MAIT) cells are a well-characterized innate-like T cell population abundant in the human liver, peripheral tissues and blood. MAIT cells serve in the first line of defense against infections, through engagement of their T cell receptor, which recognizes microbial metabolites presented on MR1, and through cytokine-mediated triggering. Typically, they show a quiescent memory phenotype but can undergo rapid up-regulation of effector functions including cytolysis upon stimulation...
February 9, 2018: Immunology and Cell Biology
Hye Ryun Yu, Yeong Jun Kim, Hye-Ra Lee
Primary effusion lymphoma (PEL), strongly linked with latent infection of Kaposi's sarcoma-associated herpesvirus (KSHV), constitutively expresses cellular interferon regulatory factor 4 (IRF4) while suppressing the expression of B cell lymphoma 6 (BCL6). Recently, it was shown that IRF4, a key transcriptional repressor of BCL6, might be a pivotal regulator of KSHV for balancing between latency and its reactivation in PEL cells. However, the action of the BCL6-IRF4 transcription factor axis during KSHV's life cycle is not clear...
February 19, 2018: Biochemical and Biophysical Research Communications
Amar H Kelkar, Kavitha S Jacob, Eman B Yousif, John J Farrell
RATIONALE: Herein, we present a case of seemingly unprovoked portal vein thrombosis (PVT) occurring in the context of an acute cytomegalovirus (CMV) infection and prolonged debilitating fatigue. PATIENT CONCERNS: A 46-year-old male airline pilot presented with a 2 week history of abdominal pain, nausea, vomiting, watery diarrhea, and daily recurrent fevers. This was in the context of progressive, debilitating fatigue for 3 months forcing the patient to leave his job...
December 2017: Medicine (Baltimore)
Juraj Koci, Quentin Bernard, Xiuli Yang, Utpal Pal
In its natural infection cycle, the pathogen of Lyme borreliosis transits between a tick vector and a mammalian host. As relatively a minor fraction of spirochetes transits between the host and the vector precluding their reliable detection at early infection, artificial membrane feeders emerged as useful tools to study roles of spirochete proteins in pathogen entry, persistence, and exit through ticks. Here we report the development of a modified membrane feeder to study the role of a Borrelia burgdorferi surface protein called Lmp1 in spirochete transitions between the murine host and ticks...
January 30, 2018: Scientific Reports
Eduardo Salinas, Arundhati Gupta, Jeffrey M Sifford, Darby G Oldenburg, Douglas W White, J Craig Forrest
Gammaherpesvirus (GHV) pathogenesis is a complex process that involves productive viral replication, dissemination to tissues that harbor lifelong latent infection, and reactivation from latency back into a productive replication cycle. Traditional loss-of-function mutagenesis approaches in mice using murine gammaherpesvirus 68 (MHV68), a model that allows for examination of GHV pathogenesis in vivo, have been invaluable for defining requirements for specific viral gene products in GHV infection. But these approaches are insufficient to fully reveal how viral gene products contribute when the encoded protein facilitates multiple processes in the infectious cycle and when these functions vary over time and from one host tissue to another...
January 24, 2018: PLoS Pathogens
Manreet Kaur Padwal, Genyang Cheng, Limin Liu, Felix J Boivin, Azim Gangji, Kenneth Scott Brimble, Darren Bridgewater, Peter J Margetts
The WNT signaling pathway is involved in wound healing and fibrosis. We evaluated the WNT signaling pathway in peritoneal membrane injury. We assessed WNT1 protein expression in the peritoneal effluents of 54 stable peritoneal dialysis (PD) patients and WNT-related gene expression in ex vivo mesothelial cell cultures from 21 PD patients. In a transforming growth factor beta (TGFB) mediated animal model of peritoneal fibrosis, we evaluated regulation of the WNT pathway and the effect of WNT inhibition on peritoneal fibrosis and angiogenesis...
January 24, 2018: American Journal of Physiology. Renal Physiology
Ashley M Groshong, Abhishek Dey, Irina Bezsonova, Melissa J Caimano, Justin D Radolf
Borrelia burgdorferi is an extreme amino acid (AA) auxotroph whose genome encodes few free AA transporters and an elaborate oligopeptide transport system (B. burgdorferi Opp [BbOpp]). BbOpp consists of five oligopeptide-binding proteins (OBPs), two heterodimeric permeases, and a heterodimeric nucleotide-binding domain (NBD). Homology modeling based on the crystal structure of liganded BbOppA4 revealed that each OBP likely binds a distinct range of peptides. Transcriptional analyses demonstrated that the OBPs are differentially and independently regulated whereas the permeases and NBDs are constitutively expressed...
December 19, 2017: MBio
David J McCulley, Mark D Wienhold, Elizabeth A Hines, Timothy A Hacker, Allison Rogers, Ryan J Pewowaruk, Rediet Zewdu, Naomi C Chesler, Licia Selleri, Xin Sun
A critical event in the adaptation to extrauterine life is relaxation of the pulmonary vasculature at birth, allowing for a rapid increase in pulmonary blood flow that is essential for efficient gas exchange. Failure of this transition leads to pulmonary hypertension (PH), a major cause of newborn mortality associated with preterm birth, infection, hypoxia, and malformations including congenital diaphragmatic hernia (CDH). While individual vasoconstrictor and dilator genes have been identified, the coordination of their expression is not well understood...
December 18, 2017: Journal of Clinical Investigation
Felicia A Tucci, Simo Kitanovski, Patricia Johansson, Ludger Klein-Hitpass, Alisan Kahraman, Jan Dürig, Daniel Hoffmann, Ralf Küppers
Patients chronically infected with hepatitis C virus (HCV) frequently develop mixed cryoglobulinemia (MC), a monoclonal expansion of IgM+ autoreactive B cells, and also have an increased B cell lymphoma risk. Whether HCV infection also impacts the B cell compartment and the B cell receptor repertoire in patients not affected by MC or lymphomas is poorly understood. Flow cytometric analysis of peripheral blood B cells of 30 MC-negative HCV-infected patients and 15 healthy controls revealed that frequencies of class-switched memory B cells were increased in the patients, whereas frequencies of transitional and naive B cells were decreased...
December 14, 2017: Blood
A Trey Belew, Caroline Junqueira, Gabriela F Rodrigues-Luiz, Bruna M Valente, Antonio Edson R Oliveira, Rafael B Polidoro, Luciana W Zuccherato, Daniella C Bartholomeu, Sergio Schenkman, Ricardo T Gazzinelli, Barbara A Burleigh, Najib M El-Sayed, Santuza M R Teixeira
Trypanosoma cruzi, the protozoan that causes Chagas disease, has a complex life cycle involving several morphologically and biochemically distinct stages that establish intricate interactions with various insect and mammalian hosts. It has also a heterogeneous population structure comprising strains with distinct properties such as virulence, sensitivity to drugs, antigenic profile and tissue tropism. We present a comparative transcriptome analysis of two cloned T. cruzi strains that display contrasting virulence phenotypes in animal models of infection: CL Brener is a virulent clone and CL-14 is a clone that is neither infective nor pathogenic in in vivo models of infection...
December 14, 2017: PLoS Pathogens
Mehrdad Tajkarimi, Hannah M Wexler
Background: While CRISPR-Cas systems have been identified in bacteria from a wide variety of ecological niches, there are no studies to describe CRISPR-Cas elements in Bacteroides species, the most prevalent anaerobic bacteria in the lower intestinal tract. Microbes of the genus Bacteroides make up ~25% of the total gut microbiome. Bacteroides fragilis comprises only 2% of the total Bacteroides in the gut, yet causes of >70% of Bacteroides infections. The factors causing it to transition from benign resident of the gut microbiome to virulent pathogen are not well understood, but a combination of horizontal gene transfer (HGT) of virulence genes and differential transcription of endogenous genes are clearly involved...
2017: Frontiers in Microbiology
Michael D Rizzo, Robert B Crawford, Joseph E Henriquez, Yasser A Aldhamen, Peter Gulick, Andrea Amalfitano, Norbert E Kaminski
OBJECTIVE: Chronic immune activation and elevated numbers of circulating activated monocytes (CD16) are implicated in HIV-associated neuroinflammation. The objective was to compare the level of circulating CD16 monocytes and IFN-γ-inducible protein 10 (IP-10) between HIV-infected cannabis users (HIV+MJ+) and noncannabis users (HIV+MJ-) and determine whether in-vitro Δ-Tetrahydrocannabinol (THC), a constituent of cannabis, affected CD16 expression as well as IP-10 production by monocytes...
February 20, 2018: AIDS
H-R Lee, Y Y Cho, G Y Lee, D-G You, Y D Yoo, Y J Kim
Hepatitis B virus X protein (HBx) acts as a multifunctional protein that regulates intracellular signalling pathways during HBV infection. It has mainly been studied in terms of its interaction with cellular proteins. Here, we show that HBx induces membrane permeabilization independently of the mitochondrial permeability transition pore complex. We generated mitochondrial outer membrane-mimic liposomes to observe the direct effects of HBx on membranes. We found that HBx induced membrane permeabilization, and the region comprising the transmembrane domain and the mitochondrial-targeting sequence was sufficient for this process...
November 28, 2017: Journal of Viral Hepatitis
P Ali, C Lefevre, B Perrouin-Verbe, L Le Normand, J Rigaud, O Bouchot, A Levesque, M-A Perrouin-Verbe
INTRODUCTION: The prevalence of bladder cancer (BC) in neurological patients seems to be similar to that of the general population. However, they are more aggressive with a higher rate of muscle-invasive forms and squamous cells carcinomas. The aim of the current study was to report etiologies, management and outcomes of BC in neurological population. MATERIAL AND METHOD: Were enrolled all neurological patients with a BC diagnosed between 2004 and 2017. The following data were retrospectively reported: age, gender, duration of the disease, mode of discovery, histological type, treatment and outcomes...
November 22, 2017: Progrès en Urologie
Wilton B Williams, Jinsong Zhang, Chuancang Jiang, Nathan I Nicely, Daniela Fera, Kan Luo, M Anthony Moody, Hua-Xin Liao, S Munir Alam, Thomas B Kepler, Akshaya Ramesh, Kevin Wiehe, James A Holland, Todd Bradley, Nathan Vandergrift, Kevin O Saunders, Robert Parks, Andrew Foulger, Shi-Mao Xia, Mattia Bonsignori, David C Montefiori, Mark Louder, Amanda Eaton, Sampa Santra, Richard Scearce, Laura Sutherland, Amanda Newman, Hilary Bouton-Verville, Cindy Bowman, Howard Bomze, Feng Gao, Dawn J Marshall, John F Whitesides, Xiaoyan Nie, Garnett Kelsoe, Steven G Reed, Christopher B Fox, Kim Clary, Marguerite Koutsoukos, David Franco, John R Mascola, Stephen C Harrison, Barton F Haynes, Laurent Verkoczy
A strategy for HIV-1 vaccine development is to define envelope (Env) evolution of broadly neutralizing antibodies (bnAbs) in infection and to recreate those events by vaccination. Here, we report host tolerance mechanisms that limit the development of CD4-binding site (CD4bs), HCDR3-binder bnAbs via sequential HIV-1 Env vaccination. Vaccine-induced macaque CD4bs antibodies neutralize 7% of HIV-1 strains, recognize open Env trimers, and accumulate relatively modest somatic mutations. In naive CD4bs, unmutated common ancestor knock-in mice Env+ B cell clones develop anergy and partial deletion at the transitional to mature B cell stage, but become Env- upon receptor editing...
November 23, 2017: Nature Communications
Gary B Evans, Peter C Tyler, Vern L Schramm
The Immucillins are chemically stable analogues that mimic the ribocation and leaving-group features of N-ribosyltransferase transition states. Infectious disease agents often rely on ribosyltransferase chemistry in pathways involving precursor synthesis for nucleic acids, salvage of nucleic acid precursors, or synthetic pathways with nucleoside intermediates. Here, we review three infectious agents and the use of the Immucillins to taget enzymes essential to the parasites. First, DADMe-Immucillin-G is a purine nucleoside phosphorylase (PNP) inhibitor that blocks purine salvage and shows clinical potential for treatment for the malaria parasite Plasmodium falciparum, a purine auxotroph requiring hypoxanthine for purine nucleotide synthesis...
February 9, 2018: ACS Infectious Diseases
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