Chlamydia Cell Biology and Pathogenesis
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C57BL/6 and 129 Inbred Mouse Strains Differ in Gbp2 and Gbp2b
Wellcome Open Research 2019, 4:124 Last updated: 30 JAN 2020 RESEARCH ARTICLE C57BL/6 and 129 inbred mouse strains differ in Gbp2 and Gbp2b expression in response to inflammatory stimuli in vivo [version 1; peer review: 2 approved] Barbara Clough 1*, Ryan Finethy2*, Rabia T. Khan1*, Daniel Fisch 1*, Sarah Jordan1, Harshil Patel 3, Jörn Coers 2,4*, Eva-Maria Frickel 1* 1Host-Toxoplasma Interaction Laboratory, The Francis Crick Institute, London, NW1 1AT, UK 2Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA 3Bioinformatics and Biostatistics, The Francis Crick Institute, London, NW1 1AT, UK 4Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA * Equal contributors First published: 20 Aug 2019, 4:124 ( Open Peer Review v1 https://doi.org/10.12688/wellcomeopenres.15329.1) Latest published: 20 Aug 2019, 4:124 ( https://doi.org/10.12688/wellcomeopenres.15329.1) Reviewer Status Abstract Invited Reviewers Background: Infections cause the production of inflammatory cytokines 1 2 such as Interferon gamma (IFNγ). IFNγ in turn prompts the upregulation of a range of host defence proteins including members of the family of version 1 guanylate binding proteins (Gbps). In humans and mice alike, GBPs restrict 20 Aug 2019 report report the intracellular replication of invasive microbes and promote inflammation. To study the physiological functions of Gbp family members, the most commonly chosen in vivo models are mice harbouring loss-of-function mutations in either individual Gbp genes or the entire Gbp gene cluster on 1 Peter Staeheli, University of Freiburg, Freiburg, mouse chromosome 3. Individual Gbp deletion strains differ in their design, Germany as some strains exist on a pure C57BL/6 genetic background, while other strains contain a 129-derived genetic interval encompassing the Gbp gene 2 Igor Kramnik , Boston University School of cluster on an otherwise C57BL/6 genetic background. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
GBP2 As a Potential Prognostic Biomarker in Pancreatic Adenocarcinoma
GBP2 as a potential prognostic biomarker in pancreatic adenocarcinoma Bo Liu1,2,3,*, Rongfei Huang4,*, Tingting Fu5, Ping He1,2, Chengyou Du3, Wei Zhou6, Ke Xu7 and Tao Ren7 1 Department of Hepatobiliary Surgery, Pidu District People's Hospital of Chengdu, Chengdu, China 2 Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Chengdu Medical College, Chengdu, China 3 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China 4 Department of Pathology, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, China 5 Department of Nosocomial Infection Control, The Third Affiliated Hospital of Chengdu Medical College, Chengdu, China 6 Department of Radiology, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, China 7 Department of Oncology, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, China * These authors contributed equally to this work. ABSTRACT Background. Pancreatic adenocarcinoma (PAAD) is a disease with atypical symptoms, an unfavorable response to therapy, and a poor outcome. Abnormal guanylate-binding proteins (GBPs) play an important role in the host's defense against viral infection and may be related to carcinogenesis. In this study, we sought to determine the relationship between GBP2 expression and phenotype in patients with PAAD and explored the possible underlying biological mechanism. Method. We analyzed the expression of GBP2 in PAAD tissues using a multiple gene expression database and a cohort of 42 PAAD patients. We evaluated GBP2's prognostic value using Kaplan–Meier analysis and the Cox regression model. GO and KEGG Submitted 13 January 2021 enrichment analysis, co-expression analysis, and GSEA were performed to illustrate the Accepted 16 April 2021 possible underlying biological mechanism. -
Product Description EN Bactoreal® Kit Chlamydiaceae
Product Description BactoReal® Kit Chlamydiaceae For research only, not for diagnostic use BactoReal® Kit Chlamydiaceae Order no. Reactions Pathogen Internal positive control DVEB03113 100 FAM channel Cy5 channel DVEB03153 50 FAM channel Cy5 channel DVEB03111 100 FAM channel VIC/HEX channel DVEB03151 50 FAM channel VIC/HEX channel Kit contents: Detection assay for Chlamydia and Chlamydophila species Detection assay for internal positive control (control of amplification) DNA reaction mix (contains uracil-N glycosylase, UNG) Positive control for Chlamydiaceae Water Background: The Chlamydiaceae family currently includes two genera and one candidate genus: genus Chlamydia (including the species Chlamydia muridarum, Chlamydia suis, Chlamydia trachomatis), genus Chlamydophila (including the species Chlamydophila abortus, Chlamydophila caviae Chlamydophila felis, Chlamydia pecorum, Chlamydophila pneumoniae, Chlamydophila psittaci), and candidatus Clavochlamydia. All Chlamydiaceae are obligate intracellular Gram-negative bacteria that cause diseases in humans and animals worldwide. Description: BactoReal® Kit Chlamydiaceae is based on the amplification and detection of the 23S rRNA gene of C. muridarum, C. suis, C. trachomatis, C. abortus, C. caviae, C. felis, C. pecorum, C. pneumoniae and C. psittaci using real-time PCR. It allows the rapid and sensitive detection of the 23S rRNA gene of Chlamydiaceae from DNA samples purified from different sample material (e.g. with the QIAamp DNA Mini Kit). For subtyping please contact ingenetix. PCR-platforms: BactoReal® Kit Chlamydiaceae is developed and validated for the ABI PRISM® 7500 instrument (Life Technologies), LightCycler® 480 (Roche) and Mx3005P® QPCR System (Agilent), but is also suitable for other real-time PCR instruments. Sensitivity and specificity: BactoReal® Kit Chlamydiaceae detects at least 10 copies/reaction. -
Modulating Antiviral Response Via CRISPR–Cas Systems
viruses Review Immunity and Viral Infections: Modulating Antiviral Response via CRISPR–Cas Systems Sergey Brezgin 1,2,3,† , Anastasiya Kostyusheva 1,†, Ekaterina Bayurova 4 , Elena Volchkova 5, Vladimir Gegechkori 6 , Ilya Gordeychuk 4,7, Dieter Glebe 8 , Dmitry Kostyushev 1,3,*,‡ and Vladimir Chulanov 1,3,5,‡ 1 National Medical Research Center of Tuberculosis and Infectious Diseases, Ministry of Health, 127994 Moscow, Russia; [email protected] (S.B.); [email protected] (A.K.); [email protected] (V.C.) 2 Institute of Immunology, Federal Medical Biological Agency, 115522 Moscow, Russia 3 Scientific Center for Genetics and Life Sciences, Division of Biotechnology, Sirius University of Science and Technology, 354340 Sochi, Russia 4 Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences, 108819 Moscow, Russia; [email protected] (E.B.); [email protected] (I.G.) 5 Department of Infectious Diseases, Sechenov University, 119991 Moscow, Russia; [email protected] 6 Department of Pharmaceutical and Toxicological Chemistry, Sechenov University, 119991 Moscow, Russia; [email protected] 7 Department of Organization and Technology of Immunobiological Drugs, Sechenov University, 119991 Moscow, Russia 8 National Reference Center for Hepatitis B Viruses and Hepatitis D Viruses, Institute of Medical Virology, Justus Liebig University of Giessen, 35392 Giessen, Germany; [email protected] * Correspondence: [email protected] † Co-first authors. Citation: Brezgin, S.; Kostyusheva, ‡ Co-senior authors. A.; Bayurova, E.; Volchkova, E.; Gegechkori, V.; Gordeychuk, I.; Glebe, Abstract: Viral infections cause a variety of acute and chronic human diseases, sometimes resulting D.; Kostyushev, D.; Chulanov, V. Immunity and Viral Infections: in small local outbreaks, or in some cases spreading across the globe and leading to global pandemics. -
Infection Genital Tract Chlamydia Muridarum Essential for Normal
The Journal of Immunology CD4+ T Cell Expression of MyD88 Is Essential for Normal Resolution of Chlamydia muridarum Genital Tract Infection Lauren C. Frazer,*,† Jeanne E. Sullivan,† Matthew A. Zurenski,† Margaret Mintus,† Tammy E. Tomasak,† Daniel Prantner,‡ Uma M. Nagarajan,† and Toni Darville*,† Resolution of Chlamydia genital tract infection is delayed in the absence of MyD88. In these studies, we first used bone marrow chimeras to demonstrate a requirement for MyD88 expression by hematopoietic cells in the presence of a wild-type epithelium. Using mixed bone marrow chimeras we then determined that MyD88 expression was specifically required in the adaptive immune compartment. Furthermore, adoptive transfer experiments revealed that CD4+ T cell expression of MyD88 was necessary for normal resolution of genital tract infection. This requirement was associated with a reduced ability of MyD882/2CD4+ T cells to accumulate in the draining lymph nodes and genital tract when exposed to the same inflammatory milieu as wild-type CD4+ T cells. We also demonstrated that the impaired infection control we observed in the absence of MyD88 could not be recapitulated by deficiencies in TLR or IL-1R signaling. In vitro, we detected an increased frequency of apoptotic MyD882/2CD4+ T cells upon activation in the absence of exogenous ligands for receptors upstream of MyD88. These data reveal an intrinsic requirement for MyD88 in CD4+ T cells during Chlamydia infection and indicate that the importance of MyD88 extends beyond innate immune responses by directly influencing adaptive immunity. The Journal of Immunology, 2013, 191: 4269–4279. hlamydia trachomatis infections of the female repro- of an adaptive immune response (19), but overly robust innate ductive tract can result in serious pathophysiology in- immune activation results in tissue damage. -
679514V2.Full.Pdf
bioRxiv preprint doi: https://doi.org/10.1101/679514; this version posted August 19, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. The large GTPase, mGBP-2, regulates Rho family GTPases to inhibit migration and invadosome formation in Triple-Negative Breast Cancer cells. Geoffrey O. Nyabuto, John P. Wilson, Samantha A. Heilman, Ryan C. Kalb, Ankita V. Abnave, and Deborah J. Vestal* Department of Biological Sciences, University of Toledo, Toledo, OH, USA 43606 *Corresponding author: Deborah J. Vestal, Department of Biological Sciences, University of Toledo, 2801 West Bancroft St., MS 1010, Toledo, OH 43606. Phone: 1-419-383-4134. FAX: 1-419-383-6228. Email: [email protected]. Running title: mGBP-2 inhibits breast cancer cell migration. Key words: Guanylate-Binding Protein, Triple-Negative Breast Cancer, migration, CDC42, Rac1. This work was supported by funding from the University of Toledo to D.J.V. Disclosure of Potential Conflicts of Interest No potential conflicts of interest were disclosed. 1 bioRxiv preprint doi: https://doi.org/10.1101/679514; this version posted August 19, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Breast cancer is the most common cancer in women. Despite advances in early detection and treatment, it is predicted that over 40,000 women will die of breast cancer in 2019. This number of women is still too high. To lower this number, more information about the molecular players in breast cancer are needed. -
CHLAMYDIOSIS (Psittacosis, Ornithosis)
EAZWV Transmissible Disease Fact Sheet Sheet No. 77 CHLAMYDIOSIS (Psittacosis, ornithosis) ANIMAL TRANS- CLINICAL FATAL TREATMENT PREVENTION GROUP MISSION SIGNS DISEASE ? & CONTROL AFFECTED Birds Aerogenous by Very species Especially the Antibiotics, Depending on Amphibians secretions and dependent: Chlamydophila especially strain. Reptiles excretions, Anorexia psittaci is tetracycline Mammals Dust of Apathy ZOONOSIS. and In houses People feathers and Dispnoe Other strains doxycycline. Maximum of faeces, Diarrhoea relative host For hygiene in Oral, Cachexy specific. substitution keeping and Direct Conjunctivitis electrolytes at feeding. horizontal, Rhinorrhea Yes: persisting Vertical, Nervous especially in diarrhoea. in zoos By parasites symptoms young animals avoid stress, (but not on the Reduced and animals, quarantine, surface) hatching rates which are blood screening, Increased new- damaged in any serology, born mortality kind. However, take swabs many animals (throat, cloaca, are carrier conjunctiva), without clinical IFT, PCR. symptoms. Fact sheet compiled by Last update Werner Tschirch, Veterinary Department, March 2002 Hoyerswerda, Germany Fact sheet reviewed by E. F. Kaleta, Institution for Poultry Diseases, Justus-Liebig-University Gießen, Germany G. M. Dorrestein, Dept. Pathology, Utrecht University, The Netherlands Susceptible animal groups In case of Chlamydophila psittaci: birds of every age; up to now proved in 376 species of birds of 29 birds orders, including 133 species of parrots; probably all of the about 9000 species of birds are susceptible for the infection; for the outbreak of the disease, additional factors are necessary; very often latent infection in captive as well as free-living birds. Other susceptible groups are amphibians, reptiles, many domestic and wild mammals as well as humans. The other Chlamydia sp. -
GBP5 Repression Suppresses the Metastatic Potential and PD-L1 Expression in Triple-Negative Breast Cancer
biomedicines Article GBP5 Repression Suppresses the Metastatic Potential and PD-L1 Expression in Triple-Negative Breast Cancer Shun-Wen Cheng 1, Po-Chih Chen 2,3,4 , Min-Hsuan Lin 5, Tzong-Rong Ger 1, Hui-Wen Chiu 5,6,7,* and Yuan-Feng Lin 5,8,* 1 Department of Biomedical Engineering, Chung Yuan Christian University, Taoyuan City 32023, Taiwan; [email protected] (S.-W.C.); [email protected] (T.-R.G.) 2 Neurology Department, Shuang-Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan; [email protected] 3 Taipei Neuroscience Institute, Taipei Medical University, New Taipei City 23561, Taiwan 4 Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan 5 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; [email protected] 6 Department of Medical Research, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan 7 TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei 11031, Taiwan 8 Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan * Correspondence: [email protected] (H.-W.C.); [email protected] (Y.-F.L.); Tel.: +886-2-22490088 (H.-W.C.); +886-2-2736-1661 (ext. 3106) (Y.-F.L.) Citation: Cheng, S.-W.; Chen, P.-C.; Abstract: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype because Lin, M.-H.; Ger, T.-R.; Chiu, H.-W.; of its high metastatic potential. Immune evasion due to aberrant expression of programmed cell Lin, Y.-F. -
Regulated Host Pathways for the Parasite Development
nature publishing group ARTICLES Eimeria falciformis infection of the mouse caecum identifies opposing roles of IFNg-regulated host pathways for the parasite development Manuela Schmid1, Emanuel Heitlinger1, Simone Spork1, Hans-Joachim Mollenkopf2, Richard Lucius1 and Nishith Gupta1,3 Intracellular parasites reprogram host functions for their survival and reproduction. The extent and relevance of parasite- mediated host responses in vivo remains poorly studied, however. We utilized Eimeria falciformis, a parasite infecting the mouse intestinal epithelium, to identify and validate host determinants of parasite infection. Most prominent mouse genes induced during the onset of asexual and sexual growth of parasite comprise interferon c (IFNc)-regulated factors, e.g., immunity-related GTPases (IRGA6/B6/D/M2/M3), guanylate-binding proteins (GBP2/3/5/6/8), chemokines (CxCL9-11), and several enzymes of the kynurenine pathway including indoleamine 2,3-dioxygenase 1 (IDO1). These results indicated a multifarious innate defense (tryptophan catabolism, IRG, GBP, and chemokine signaling), and a consequential adaptive immune response (chemokine-cytokine signaling and lymphocyte recruitment). The inflammation- and immunity-associated transcripts were increased during the course of infection, following influx of B cells, Tcells, and macrophages to the parasitized caecum tissue. Consistently, parasite growth was enhanced in animals inhibited for CxCr3, a major receptor for CxCL9-11 present on immune cells. Interestingly, despite a prominent induction, mouse IRGB6 failed to bind and disrupt the parasitophorous vacuole, implying an immune evasion by E. falciformis. Furthermore, oocyst output was impaired in IFNc-R À / À and IDO1 À / À mice, both of which suggest a subversion of IFNc signaling by the parasite to promote its growth. -
Engineered Type 1 Regulatory T Cells Designed for Clinical Use Kill Primary
ARTICLE Acute Myeloid Leukemia Engineered type 1 regulatory T cells designed Ferrata Storti Foundation for clinical use kill primary pediatric acute myeloid leukemia cells Brandon Cieniewicz,1* Molly Javier Uyeda,1,2* Ping (Pauline) Chen,1 Ece Canan Sayitoglu,1 Jeffrey Mao-Hwa Liu,1 Grazia Andolfi,3 Katharine Greenthal,1 Alice Bertaina,1,4 Silvia Gregori,3 Rosa Bacchetta,1,4 Norman James Lacayo,1 Alma-Martina Cepika1,4# and Maria Grazia Roncarolo1,2,4# Haematologica 2021 Volume 106(10):2588-2597 1Department of Pediatrics, Division of Stem Cell Transplantation and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, USA; 2Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, USA; 3San Raffaele Telethon Institute for Gene Therapy, Milan, Italy and 4Center for Definitive and Curative Medicine, Stanford School of Medicine, Stanford, CA, USA *BC and MJU contributed equally as co-first authors #AMC and MGR contributed equally as co-senior authors ABSTRACT ype 1 regulatory (Tr1) T cells induced by enforced expression of interleukin-10 (LV-10) are being developed as a novel treatment for Tchemotherapy-resistant myeloid leukemias. In vivo, LV-10 cells do not cause graft-versus-host disease while mediating graft-versus-leukemia effect against adult acute myeloid leukemia (AML). Since pediatric AML (pAML) and adult AML are different on a genetic and epigenetic level, we investigate herein whether LV-10 cells also efficiently kill pAML cells. We show that the majority of primary pAML are killed by LV-10 cells, with different levels of sensitivity to killing. Transcriptionally, pAML sensitive to LV-10 killing expressed a myeloid maturation signature. -
Discovery of Genetic Correlates Important for Chlamydia Infection and Pathogenesis
DISCOVERY OF GENETIC CORRELATES IMPORTANT FOR CHLAMYDIA INFECTION AND PATHOGENESIS By Kelly S. Harrison Submitted to the graduate degree program in Molecular Biosciences and the Graduate Faculty of the University of Kansas in partial fulfillment of the requirements for the degree Doctor of Philosophy. _________________________________ Chairperson (P. Scott Hefty, Ph.D.) ________________________________* (Lynn E. Hancock, Ph.D.) ________________________________* (Susan M. Egan, Ph.D.) ________________________________* (David J. Davido, Ph.D.) ________________________________* (Mario Rivera, Ph.D.) *Committee Members Date Defended: July 5th 2017 The Dissertation Committee for Kelly S. Harrison certifies that this is the approved version of the following dissertation: DISCOVERY OF GENETIC CORRELATES IMPORTANT FOR CHLAMYDIA INFECTION AND PATHOGENESIS _________________________________ Chairperson (P. Scott Hefty, Ph.D.) Date Approved: July 25th, 2017 ii ABSTRACT Chlamydia species are responsible for over 1.2 million reports of bacterial sexually transmitted infections in the United States; a number that has been steadily increasing for the past decade. Worldwide, a cumulative 131 million new cases of Chlamydia trachomatis are estimated among individuals between ages 15-49. In most individuals, chlamydial infections are asymptomatic, resulting in long-term sequelae such as pelvic inflammatory disease, salpingitis and infertility. Along with genitourinary infections, Chlamydia is also the leading cause of blinding trachoma, affecting nearly 1.9 million people across 42 different countries. While current treatment with antibiotics remains successful in combating infections, evidence of persistent infections, acquisition of antibiotic resistances, and recurring exposure intensifies the necessity for enhanced prophylactic approaches, including the development of a vaccine. In order to develop these advances, species-specific targets, as well as mechanisms the bacterium uses to establish infection must be identified.