DOCSLIB.ORG

Inflammatory Responses in Mice After Intratracheal Instillation of Microbes Isolated from Moldy Buildings

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Inflammatory Responses in Mice After Intratracheal Instillation of Microbes Isolated from Moldy Buildings View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Julkari Inflammatory Responses in Mice after Intratracheal Instillation of Microbes Isolated from Moldy Buildings Juha J. Jussila National Public Health Institute Division of Environmental Health Laboratory of Toxicology P.O.Box 95, FIN-70701 Kuopio, FINLAND and University of Kuopio Department of Pharmacology and Toxicology P.O.Box 1627, FIN-70211 Kuopio, FINLAND Academic dissertation To be presented with permission of the Faculty of Pharmacy of the University of Kuopio for public examination in Auditorium L3 in the Canthia building, University of Kuopio, on Friday 24th January 2003, at 12 o’clock noon. Publisher: National Public Health Institute Mannerheimintie 166 FIN-00300 Helsinki FINLAND Phone +358-9-47441 Fax +358-7-47448408 Author’s address: National Public Health Institute Division of Environmental Health Department of Environmental Medicine Laboratory of Toxicology P.O.Box 95 FIN-70701 Kuopio FINLAND Phone +358-17-201320 Fax +358-17-201265 Email [email protected] Supervisors: Docent Maija-Riitta Hirvonen, Ph.D. Department of Environmental Health National Public Health Institute, Kuopio, Finland Docent Hannu Komulainen, Ph.D. (Pharm.) Department of Environmental Health National Public Health Institute, Kuopio, Finland Professor Jukka Pelkonen, M.D. Department of Clinical Microbiology University of Kuopio, Kuopio, Finland Reviewers: Professor Pekka Saikku, M.D. Department of Medical Microbiology University of Oulu, Oulu, Finland Docent Ilkka Julkunen, M.D. Department of Microbiology National Public Health Institute, Helsinki, Finland Opponent: Professor Kai Savolainen, M.D., Ph.D. Department of Industrial Hygiene and Toxicology Finnish Institute of Occupational Health, Helsinki, Finland ISBN 951-740-331-3 ISSN 0359-3584 ISBN (pdf version) 951-740-332-1 ISSN (pdf version) 1458-6290 Kuopio University Printing Office, Kuopio, Finland, 2003 Jussila, Juha J. Inflammatory Responses in Mice after Intratracheal Instillation of Microbes Isolated from Moldy Buildings. Publications of the National Public Health Institute, A1/2003, 96 pages. ISBN 951-740-331-3 ISSN 0359-3584 ISBN (pdf version) 951-740-332-1 ISSN (pdf version) 1458-6290 ABSTRACT Moisture-damage is common in buildings, and it is associated with a variety of adverse health effects, especially inflammatory responses in the lower airways. Exposure to microbial spores or cells has been suspected to be one reason for the inflammation, but the inflammatory and toxic potential of the microbes has not been well characterized. In this study, a mouse model was devised to elucidate and compare the adverse effects provoked by microbes isolated from the indoor air of a moisture-damaged building. The animals were exposed intratracheally to the microbial spores or cells. The effects caused by the bacterial species Streptomyces californicus and Mycobacterium terrae and the fungi Aspergillus versicolor and Penicillium spinulosum were investigated. They are typical microbes observed in moisture-damaged buildings, but P. spinulosum is also frequently observed in all indoor air environments. Both the dose-response and time-course of the inflammatory and toxic responses were investigated after a single dose of the microbe. Biochemical parameters indicating inflammation and/or toxicity (tumor necrosis factor α, TNFα, interleukin-6, IL-6, total protein, albumin, hemoglobin and lactate dehydrogenase) were measured from bronchoalveolar lavage fluid (BALF), and a histopathological analysis was performed from lungs, lymph nodes and spleen. In addition, inducible nitric oxide synthase (iNOS) was determined from lavaged cells, and the cytokine concentrations were measured in serum. Moreover, the effects of S. californicus were studied after repeated dosing of the spores. In that experiment also lymphocyte subpopulations were investigated in the lungs, lymph nodes and the spleen. Both the biochemical parameters and histopathology revealed that all the microbes studied provoked inflammation after a single dose, but the magnitude and its characteristic features were different. The spores of S. californicus provoked a very intense acute inflammation indicated by a strong and rapid IL-6 and TNFα production in the lungs, recruitment of inflammatory cells into the airways, and expression of inducible nitric oxide synthase (iNOS) in lavaged cells at 24 hours. An increase in TNFα and IL-6 concentrations in serum was also detected. The cells of M. terrae induced a biphasic inflammatory response, which consisted of an acute and a sustained phase. In the acute phase, TNFα and IL-6 were produced and inflammatory cells were recruited into the lungs. In the later phase, TNFα production was sustained up to 14 days, and inflammatory cell recruitment was even more intense, with iNOS being expressed in lavaged cells. Reactive changes in lymph nodes were also observed. The inflammatory response lasted until the end of the experiment (28 days), and at that time some mycobacterial cells were still present in the lungs. At comparable volumetric doses with the bacteria, the fungal species also induced a rapid production of proinflammatory cytokines, and inflammatory cell recruitment into the airways, but they were generally less potent than the bacteria. P. spinulosum induced only a mild inflammatory response and transient TNFα and IL-6 production into BALF. The spores of A. versicolor caused a slow TNFα response, and the inflammatory cell response was more sustained than by P. spinulosum. In contrast to the bacteria, the studied fungal species did not induce expression of iNOS. Acute cytotoxicity in lungs indicated by LDH response was observed during S. californicus, M. terrae and A. versicolor exposure. M. terrae exposure caused the strongest and most sustained effect. However, none of the microbes were highly cytotoxic in the lungs, and the effect was frequently associated with an acute inflammatory response. P. spinulosum exposure showed no cytotoxic effect. After repeated airway exposure to the spores of S. californicus, both the innate and adaptive host defenses were activated in the lungs. The inflammatory cell response in the lungs was more severe and appeared at a lower dose level than after a single dose. Spleen cell count was decreased indicating a systemic immunotoxic effect, and the lymphocyte subpopulations were altered in the lungs, lymph nodes and the spleen. Reactive changes were observed in lymph node histopathology. In summary, the results show that the indicated microbes have a different potential to cause inflammatory and toxic responses after airway exposure in mice, and suggest that microbes present in a moisture-damaged building can induce inflammation in lungs and cause systemic toxicity. To my family ACKNOWLEDGEMENTS This work has been carried out in the Laboratory of Toxicology, Department of Environmental Health, National Public Health Institute, Kuopio, Finland. I would like to thank Professor Jouko Tuomisto, the Director of the Department of Environmental Health, for providing the facilities for this study. I express my deepest gratitude to my principal supervisor Docent Maija-Riitta Hirvonen for her enthusiastic attitude, and support throughout this work. I also wish to express my warmest thanks to Docent Hannu Komulainen for his valuable guidance and advice, and Professor Jukka Pelkonen for his encouragement and guidance during these years. Thank you Jukka also for the hard badminton games and pleasant discussions. My kind appreciation is due to Docent Aino Nevalainen and Ph.D. Anne Hyvärinen for their enthusiastic attitude concerning the moldy building phenomenon, and valuable collaboration. I am also grateful to Ph.D. Eila Torvinen and M.Sc. Pirjo Torkko for providing the mycobacterium for the experiments, and their comments concerning the manuscript. I also wish to express my warmest thanks to Professor Veli-Matti Kosma for his valuable comments about the manuscripts, and excellent co-operation. I owe my deepest thanks to the reviewers Professor Pekka Saikku and Docent Ilkka Julkunen for their constructive criticism, beneficial advice, and positive co-operation. I want to thank my nearest co-workers M.Sc. Kati Huttunen and Ph.D. Marjut Roponen for their company, sense of humor, and excellent co-operation during these years in the same office room. I wish to thank also M.Sc. Timo Murtoniemi for his friendship and support. I am also grateful to Ph.D. Arja Hälinen, Dr. Raimo O. Salonen, Dr. Stephen H. Gavett and Dr. Carol Rao, Docent Anita Naukkarinen, and Ph.D. Jenni Vuola for consultation, and co- operation during this study. I thank also Jorma Mäki-Paakkanen for his valuable contribution concerning genotoxicological analyses, as well as his sense of humor. My special thanks are due to Mrs. Leena Heikkinen for her excellent technical assistance, pleasant company and friendship during the long days in the laboratory. I owe my warmest thanks to Ms. Heli Martikainen for her excellent technical assistance, including also the field of cell culturing. I also wish to thank the late Mrs. Tuula Wallenius, Ms. Mirja Ojainväli, Mrs. Arja Rönkkö, Mrs. Anne Seppä, Mrs. Irma Väänänen and Mrs. Arja Kinnunen for their excellent technical assistance and co-operation. I owe my sincere thanks to M.Sc. Mikko Vahteristo and M.Sc. Pekka Tiittanen for their valuable statistical consultation, and friendship during these years. I wish to thank also Pharm.D. Ewen MacDonald for checking the language of the manuscripts,
Load more

Recommended publications
  • Isolation of Fungal Cellulase Gene Transcript from Penicillium Spinulosum
    Isolation of fungal cellulase gene transcript from Penicillium spinulosum A Master’s Thesis Presented to the faculty of The College of Science and Mathematics Colorado State University – Pueblo In Partial Fulfillment of the requirements for the degree of Master of Science in Biochemistry By Srivatsan Parthasarathy Colorado State University – Pueblo May, 2018 ACKNOWLEDGEMENTS I would like to thank my research mentor Dr. Sandra Bonetti for guiding me through my research thesis and helping me in difficult times during my Master’s degree. I would like to thank Dr. Dan Caprioglio for helping me plan my experiments and providing the lab space and equipment. I would like to thank the department of Biology and Chemistry for supporting me through assistantships and scholarships. I would like to thank my wife Vaishnavi Nagarajan for the emotional support that helped me complete my degree at Colorado State University – Pueblo. III TABLE OF CONTENTS 1) ACKNOWLEDGEMENTS …………………………………………………….III 2) TABLE OF CONTENTS …………………………………………………….....IV 3) ABSTRACT……………………………………………………………………..V 4) LIST OF FIGURES……………………………………………………………..VI 5) LIST OF TABLES………………………………………………………………VII 6) INTRODUCTION………………………………………………………………1 7) MATERIALS AND METHODS………………………………………………..24 8) RESULTS………………………………………………………………………..50 9) DISCUSSION…………………………………………………………………….77 10) REFERENCES…………………………………………………………………...99 11) THESIS PRESENTATION SLIDES……………………………………………...113 IV ABSTRACT Cellulose and cellulosic materials constitute over 85% of polysaccharides in landfills. Cellulose is also the most abundant organic polymer on earth. Cellulose digestion yields simple sugars that can be used to produce biofuels. Cellulose breaks down to form compounds like hemicelluloses and lignins that are useful in energy production. Industrial cellulolysis is a process that involves multiple acidic and thermal treatments that are harsh and intensive.
    [Show full text]
  • INVITED SPEAKERS (INV) Presentation: Monday, September 28, 2015 from 10:30 – 11:00 in Room Congress Saal
    INVITED SPEAKERS (INV) Presentation: Monday, September 28, 2015 from 10:30 – 11:00 in room Congress Saal. INV01 Redefining Virulence: Bacterial Gene Expression during INV03 Human Infection Breath-taking viral zoonosis: Lessons from influenza viruses H. L. T. Mobley T. Wolff University of Michigan Medical School, Department of Robert Koch-Institut, Division 17, Influenza viruses and other Microbiology and Immunology, Ann Arbor, United States Respiratory Viruses, Berlin, Germany Investigators identifying virulence genes at first did so by The World Health Organization recently expressed concerns about examining transposon mutants or individual gene mutations. an unprecedented diversity and geographical distribution of Mutants of bacterial pathogens were then assessed in animals, influenza viruses currently circulating in animal reservoirs. This whose symptoms mimicked human disease. Later, genome-wide includes an increase in the detection of animal influenza viruses screens (STM, IVET, IVIAT) were developed whereby genes and that co-circulate and exchange viral genes giving rise to novel virus proteins that influence virulence could be identified. These efforts strains. As the avian and porcine host reservoirs have in the past led to our conventional view of microbial virulence, with its focus contributed essentially to the genesis of human pandemic influenza on adhesins, iron acquisition, toxins, secretion, and motility, as viruses causing waves of severe respiratory disease on a global well as on those bacteria with genes such as on horizontally scale, this is a notable situation. transferred pathogenicity-associated islands that are not found in Zoonotic transmissions of avian influenza viruses belonging to the commensal strains. Now, however, we also must consider what H5N1 or H7N9 subtypes have been well documented in recent metabolic pathways are in play when microbial pathogens infect years.
    [Show full text]
  • | Hao Wanatha Maria Del Contatta Datum
    |HAO WANATHA MARIAUS009844679B2 DEL CONTATTA DATUM (12 ) United States Patent ( 10 ) Patent No. : US 9 ,844 , 679 B2 Nayfach - Battilana ( 45 ) Date of Patent : * Dec . 19 , 2017 (54 ) NANOPARTICLE - SIZED MAGNETIC (56 ) References Cited ABSORPTION ENHANCERS HAVING THREE - DIMENSIONAL GEOMETRIES U . S . PATENT DOCUMENTS ADAPTED FOR IMPROVED DIAGNOSTICS 4 , 106 ,488 A 8 / 1978 Gordon AND HYPERTHERMIC TREATMENT 4 ,303 ,636 A 12/ 1981 Gordon ( 71 ) Applicant: Qteris, Inc. , San Rafael, CA (US ) ( Continued ) ( 72 ) Inventor : Joseph N . Nayfach - Battilana , San FOREIGN PATENT DOCUMENTS Rafael , CA (US ) EP 0040512 B1 11 / 1981 EP 0136530 A16 /1988 (73 ) Assignee : Qteris, Inc. , San Rafael , CA (US ) (Continued ) ( * ) Notice : Subject to any disclaimer , the term of this patent is extended or adjusted under 35 OTHER PUBLICATIONS U . S . C . 154 ( b ) by 903 days. “ Krishna et al ., Unusual size -dependent magnetization in near This patent is subject to a terminal dis hemispherical Co nanomagnets on SiO . sub . 2 from fast pulsed laser claimer . processing” , J . Appl. Phys. 103 , 073902 (2008 ) (“ Krishna ” ) .* (Continued ) ( 21 ) Appl . No .: 14 /044 , 251 Primary Examiner — Joseph Stoklosa (22 ) Filed : Oct. 2 , 2013 Assistant Examiner — Adam Avigan (74 ) Attorney , Agent, or Firm — Marek Alboszta (65 ) Prior Publication Data US 2014 /0172049 A1 Jun . 19 , 2014 (57 ) ABSTRACT Nanoparticle- sized magnetic absorption enhancers (MAES ) Related U . S . Application Data exhibiting a controlled response to a magnetic field , includ ing a controlled mechanical response and an inductive (62 ) Division of application No . 12 /925 ,904 , filed on Nov. thermal response . The MAEs have a magnetic material that 1 , 2010 , now Pat .
    [Show full text]
  • Rope Parasite” the Rope Parasite Parasites: Nearly Every AuSC Child I Ever Treated Proved to Carry a Significant Parasite Burden
    Au#sm: 2015 Dietrich Klinghardt MD, PhD Infec4ons and Infestaons Chronic Infecons, Infesta#ons and ASD Infec4ons affect us in 3 ways: 1. Immune reac,on against the microbes or their metabolic products Treatment: low dose immunotherapy (LDI, LDA, EPD) 2. Effects of their secreted endo- and exotoxins and metabolic waste Treatment: colon hydrotherapy, sauna, intes4nal binders (Enterosgel, MicroSilica, chlorella, zeolite), detoxificaon with herbs and medical drugs, ac4vaon of detox pathways by solving underlying blocKages (methylaon, etc.) 3. Compe,,on for our micronutrients Treatment: decrease microbial load, consider vitamin/mineral protocol Lyme, Toxins and Epigene#cs • In 2000 I examined 10 au4s4c children with no Known history of Lyme disease (age 3-10), with the IgeneX Western Blot test – aer successful treatment. 5 children were IgM posi4ve, 3 children IgG, 2 children were negave. That is 80% of the children had clinical Lyme disease, none the history of a 4cK bite! • Why is it taking so long for au4sm-literate prac44oners to embrace the fact, that many au4s4c children have contracted Lyme or several co-infec4ons in the womb from an oVen asymptomac mother? Why not become Lyme literate also? • Infec4ons can be treated without the use of an4bio4cs, using liposomal ozonated essen4al oils, herbs, ozone, Rife devices, PEMF, colloidal silver, regular s.c injecons of artesunate, the Klinghardt co-infec4on cocKtail and more. • Symptomac infec4ons and infestaons are almost always the result of a high body burden of glyphosate, mercury and aluminum - against the bacKdrop of epigene4c injuries (epimutaons) suffered in the womb or from our ancestors( trauma, vaccine adjuvants, worK place related lead, aluminum, herbicides etc., electromagne4c radiaon exposures etc.) • Most symptoms are caused by a confused upregulated immune system (molecular mimicry) Toxins from a toxic environment enter our system through damaged boundaries and membranes (gut barrier, blood brain barrier, damaged endothelium, etc.).
    [Show full text]
  • Identification and Nomenclature of the Genus Penicillium
    Downloaded from orbit.dtu.dk on: Dec 20, 2017 Identification and nomenclature of the genus Penicillium Visagie, C.M.; Houbraken, J.; Frisvad, Jens Christian; Hong, S. B.; Klaassen, C.H.W.; Perrone, G.; Seifert, K.A.; Varga, J.; Yaguchi, T.; Samson, R.A. Published in: Studies in Mycology Link to article, DOI: 10.1016/j.simyco.2014.09.001 Publication date: 2014 Document Version Publisher's PDF, also known as Version of record Link back to DTU Orbit Citation (APA): Visagie, C. M., Houbraken, J., Frisvad, J. C., Hong, S. B., Klaassen, C. H. W., Perrone, G., ... Samson, R. A. (2014). Identification and nomenclature of the genus Penicillium. Studies in Mycology, 78, 343-371. DOI: 10.1016/j.simyco.2014.09.001 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. available online at www.studiesinmycology.org STUDIES IN MYCOLOGY 78: 343–371. Identification and nomenclature of the genus Penicillium C.M.
    [Show full text]
  • Gram Positive Bacteria.Pdf
    Taxonomy of gram-positive bacteria High G+C content in DNA Low G+C content in DNA Actinobacteria Firmicutes Molicutes • Actinomyces • Bacillus • Mycoplasma • Streptomyces • Clostridium • Ureaplasma • Nocardia • Lactobacillus • Acholeplasma • Corynebcaterium • Listeria • Mycobacterium • Erysipelothrix • Micrococcus • Staphylococcus • Propionibacterium • Gardnerella • Streptococcus • Bifidobacterium • Enterococcus Actinomyces • Hypha-like filamentous cells • Facultatively anaerobic/anaerobic, • Commensal of skin • Grow slowly, prefer anaerobic condition A. israelii – actinomycosis – cervicofacial (poor oral hygiene, invasive dental procedure) thoracic, abdominal, pelvic, CNS -abscesses • Treatment – penicillin, erythromycin, clindamycin prolonged therapy (4-12 m) Nocardia • Strict aerobic rods • Cell wall – mycolic acids, arabinosa, galactose, meso-diaminopimelic acid weakly acid –fast • N. asteroides, N. brasiliensis • Bronchopulmonary disease (immunocompromised patiants) • Cutaneous infections – mycetoma, lymphocutaneous i., cellulitis, abscesses • Treatment – sulfonamides, 6 w., surgery Corynebacterium • Cell wall with short mycolic acids, meso-DAP, arabinose, galactose • Metachomatic granules • Aerobic, facultativly anaerobic, non motile • Associated wit human disease: • C. diphtheriae, C. jejkeium, C. urealiticum, Corynebacterium diphtheriae • Diphtheria – bacteria infected with β-phage • Diphtheria toxin – AB toxin, inhibits protein synthesis by inactivating EF-2 • Pediatric disease – respiratory diphtheria, • Sore throat, low-grade
    [Show full text]
  • Identification and Nomenclature of the Genus Penicillium
    available online at www.studiesinmycology.org STUDIES IN MYCOLOGY 78: 343–371. Identification and nomenclature of the genus Penicillium C.M. Visagie1, J. Houbraken1*, J.C. Frisvad2*, S.-B. Hong3, C.H.W. Klaassen4, G. Perrone5, K.A. Seifert6, J. Varga7, T. Yaguchi8, and R.A. Samson1 1CBS-KNAW Fungal Biodiversity Centre, Uppsalalaan 8, NL-3584 CT Utrecht, The Netherlands; 2Department of Systems Biology, Building 221, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark; 3Korean Agricultural Culture Collection, National Academy of Agricultural Science, RDA, Suwon, Korea; 4Medical Microbiology & Infectious Diseases, C70 Canisius Wilhelmina Hospital, 532 SZ Nijmegen, The Netherlands; 5Institute of Sciences of Food Production, National Research Council, Via Amendola 122/O, 70126 Bari, Italy; 6Biodiversity (Mycology), Agriculture and Agri-Food Canada, Ottawa, ON K1A0C6, Canada; 7Department of Microbiology, Faculty of Science and Informatics, University of Szeged, H-6726 Szeged, Közep fasor 52, Hungary; 8Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8673, Japan *Correspondence: J. Houbraken, [email protected]; J.C. Frisvad, [email protected] Abstract: Penicillium is a diverse genus occurring worldwide and its species play important roles as decomposers of organic materials and cause destructive rots in the food industry where they produce a wide range of mycotoxins. Other species are considered enzyme factories or are common indoor air allergens. Although DNA sequences are essential for robust identification of Penicillium species, there is currently no comprehensive, verified reference database for the genus. To coincide with the move to one fungus one name in the International Code of Nomenclature for algae, fungi and plants, the generic concept of Penicillium was re-defined to accommodate species from other genera, such as Chromocleista, Eladia, Eupenicillium, Torulomyces and Thysanophora, which together comprise a large monophyletic clade.
    [Show full text]
  • IDSA Guidelines for Preclinical Microbiology and Infectious Diseases
    IDSA Guidelines for Preclinical Microbiology and Infectious Diseases Frederick Southwick,M.D., Peter Katona, M.D., Carol Kauffman, M.D., Sara Monroe, M.D., Liise-anne Pirofski, M.D., Carlos del Rio, M.D., Harry Gallis, M.D., and William Dismukes, M.D. Key Facts and Concepts in Microbiology and Infectious Diseases Viral Infections Editorial comment: A major problem for most of the viruses is that many have similar clinical presentations, making case-based teaching somewhat more difficult. But examples of viruses primarily attacking different organ systems may prove helpful. Also distinct skin rashes should be shown to allow the students to become familiar with characteristic skin lesions of measles, small pox, chicken pox (varicella), rubella, and herpes simplex and other human herpes viruses. 1. Structure and Classification A. Nucleic acid – multiple forms • RNA viruses . Single stranded + RNA (polio, West Nile) . Single stranded – RNA requires viral RNA polymerase to synthesize + mRNA (influenza, measles) . Double stranded RNA requires viral RNA polymerase (rotavirus) . Single stranded +RNA to DNA incorporated into host cell genome, requires a viral reverse transcriptase (retroviruses, HIV) • DNA viruses, with the exception of pox viruses all require host RNA polymerase . Single-stranded DNA (parvoviruses) . Double stranded linear DNA viruses (herpesviruses, adenovirus) . Double stranded circular DNA (hepadnaviruses, papillomaviruses) B. Capsid formation 2. Life cycles and Pathogenesis – review of different strategies used by viruses • Enveloped . Matrix (M) protein . Spike formation . Budding • Nonenveloped . Apoptosis . Cell lysis 3. Epidemiology • Secretions: aerosolization, hand to mucous membranes • Transcutaneous • Fecal-oral • Sexual • Hematogenous (blood transfusions, needle sticks) • Arthropodborne 4. Sites of infection and types of disease caused • Respiratory tract • Gastrointestinal tract and liver • Skin • Nervous system 5.
    [Show full text]
  • DGCR8 Deficiency Impairs Macrophage Growth and Unleashes
    Published Online: 26 March, 2021 | Supp Info: http://doi.org/10.26508/lsa.202000810 Downloaded from life-science-alliance.org on 2 October, 2021 Research Article DGCR8 deficiency impairs macrophage growth and unleashes the interferon response to mycobacteria Barbara Killy1 , Barbara Bodendorfer1,Jorg¨ Mages2 , Kristina Ritter3, Jonathan Schreiber1 , Christoph Holscher¨ 3,4, Katharina Pracht5 , Arif Ekici6 , Hans-Martin Jack¨ 5, Roland Lang1 The mycobacterial cell wall glycolipid trehalose-6,6-dimycolate STAT1 and IRF5 and thereby suppresses type I IFN responses (Tang (TDM) activates macrophages through the C-type lectin receptor et al, 2009). Further important miRNAs controlling innate immune MINCLE. Regulation of innate immune cells relies on miRNAs, which responses are miR-21, miR-125b, and miR-142-3p, which impair may be exploited by mycobacteria to survive and replicate in translation of the adapter protein MYD88 (Xue et al, 2017) and macrophages. Here, we have used macrophages deficient in the regulate mRNA levels of the pro-inflammatory cytokines TNF and microprocessor component DGCR8 to investigate the impact of IL-6 (Rajaram et al, 2011; Liu et al, 2016). In contrast, miR-155 pro- miRNAontheresponsetoTDM.DeletionofDGCR8inbonemarrow motes inflammatory immune responses by attenuating the expression progenitors reduced macrophage yield, but did not block macro- of key negative regulators, including the inhibitor of IFN signaling SOCS1 phage differentiation. DGCR8-deficient macrophages showed re- (Yao et al, 2012; Chen et al, 2013; Li et al, 2013; Rao et al, 2014)andthe duced constitutive and TDM-inducible miRNA expression. RNAseq phosphatase SHIP1 (Wang et al, 2014). Thus, miRNAs represent a fun- analysis revealed that they accumulated primary miRNA transcripts damental regulatory layer in innate immune responses by fine-tuning and displayed a modest type I IFN signature at baseline.
    [Show full text]
  • Analysis of Various Bioreactor Configurations for Heavy Metal Removal Using the Fungus Penicillium Ochro-Chloron
    ANALYSIS OF VARIOUS BIOREACTOR CONFIGURATIONS FOR HEAVY METAL REMOVAL USING THE FUNGUS PENICILLIUM OCHRO-CHLORON A Thesis Submitted to the Faculty of WORCESTER POLYTECHNIC INSITUTE in partial fulfillment of the requirements for the Degree of Master of Science in Biology by Eva Lotta Andersson May 1999 Approved: Dr. Alexander A. DiIorio, Major Advisor Dr. Theodore C. Crusberg, Thesis Advisor Dr. Ronald D. Cheetham, Head of Department Abstract Penicillium ochro-chloron (ATCC strain # 36741), a filamentous fungus with the capability for removing copper ions from aqueous solutions, was studied as a possible biological trap (biotrap) for remediation of heavy metal contaminants in industrial wastewaters. This research demonstrated that in shake flasks the fungus removed copper from surrogate wastewater with 100mg/L copper contamination by as much as 99%. These results did not translate to the bioreactor configuration of a packed bed column, as channeling occurred through the bed, shown by conductivity tracer studies. A fluidized bed configuration was studied and resulted in copper removal of 97%, with a capacity of 149 mg[Cu]/g dry weight biomass, under the conditions of 50% dissolved oxygen. For dissolved oxygen concentrations below the critical oxygen concentration for the fungus (20% saturation) there was minimal copper removal. Mixing studies in the fluidized bed reactor showed that the system was diffusion limited. Mathematical modeling using first order kinetics associated with diffusion limited reactions resulted in rate constants for Cu2+ uptake of approximately 0.031 h-1, which were dependent on the dissolved oxygen concentration. Modeling of the reaction with a second order kinetic equation showed that there are possibly factors regulating copper uptake besides oxygen.
    [Show full text]
  • Penicillium Species Endophytic in Coffee Plants and Ochratoxin a Production
    Mycologia, 98(1), 2006, pp. 31–42. # 2006 by The Mycological Society of America, Lawrence, KS 66044-8897 Penicillium species endophytic in coffee plants and ochratoxin A production Fernando E. Vega1 endophytes have been conducted in dozens of plants, Francisco Posada including many important agricultural commodities Insect Biocontrol Laboratory, U.S. Department of such as wheat (Larran et al 2002a), bananas (Poca- Agriculture, Agricultural Research Service, Bldg. 011A, sangre et al 2000, Cao et al 2002), soybeans (Larran et BARC-W, Beltsville, Maryland 20705 al 2002b) and tomatoes (Larran et al 2001), but Stephen W. Peterson coffee endophytes remain largely unexplored with Microbial Genomics and Bioprocessing Research Unit, the exception of bacterial endophytes (Vega et al National Center for Agricultural Utilization Research, 2005). U.S. Department of Agriculture, Agricultural Research Several species of Penicillium were isolated as part Service, 1815 N. University St., Peoria, Illinois 61604 of a large survey for fungal endophytes in coffee Thomas J. Gianfagna (Vega et al in prep). Members of this genus produce Fabio Chaves a variety of metabolites (Mantle 1987, Abramson Department of Biology and Pathology, Rutgers The State 1997, Samson and Frisvad 2004), and contamination University of New Jersey, 59 Dudley Road, New with one of these metabolites, ochratoxin A (OTA), Brunswick, New Jersey 08903 can be a problem in many commodities, including coffee (Bucheli and Taniwaki 2002), due to its possible adverse effect on human health. Species of Abstract: Tissues from Coffea arabica, C. congensis, C. Aspergillus are the main OTA producers in tropical dewevrei and C. liberica collected in Colombia, Hawaii and semi-tropical areas (Abramson 1997).
    [Show full text]
  • Fungi and Allergic Lower Respiratory Tract Diseases
    Clinical reviews in allergy and immunology Series editors: Donald Y. M. Leung, MD, PhD, and Dennis K. Ledford, MD Fungi and allergic lower respiratory tract diseases Alan P. Knutsen, MD,a Robert K. Bush, MD,b Jeffrey G. Demain, MD,c David W. Denning, FRCP, FMedSci,d Anupma Dixit, PhD, MPH,e Abbie Fairs, MD,f Paul A. Greenberger, MD,g Barbara Kariuki, BS, MPH,a Hirohito Kita, MD,h Viswanath P. Kurup, PhD,i Richard B. Moss, MD,j Robert M. Niven, MD,d Catherine H. Pashley, MD,f Raymond G. Slavin, MD,e Hari M. Vijay, PhD, MPH,k and Andrew J. Wardlaw, MDf St Louis, Mo, Madison and Milwaukee, Wis, Anchorage, Alaska, Manchester and Leicester, United Kingdom, Chicago, Ill, Rochester, Minn, Palo Alto, Calif, and Ottawa, Ontario, Canada INFORMATION FOR CATEGORY 1 CME CREDIT Credit can now be obtained, free for a limited time, by reading the review PhD, Richard B. Moss, MD, Robert M. Niven, MD, Catherine H. Pashley, articles in this issue. Please note the following instructions. MD, Raymond G. Slavin, MD, Hari M. Vijay, PhD, MPH, and Andrew J. Method of Physician Participation in Learning Process: The core ma- Wardlaw, MD terial for these activities can be read in this issue of the Journal or online at Activity Objectives the JACI Web site: www.jacionline.org. The accompanying tests may only 1. To describe the most common environmental factors affecting fungal be submitted online at www.jacionline.org. Fax or other copies will not be spore dispersal . accepted. 2. To list the diagnostic criteria for allergic bronchopulmonary aspergil- Date of Original Release: February 2012.
    [Show full text]