Immunomodulation through excretory-secretory products of the parasitic helminth Echinococcus multilocularis:
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| Format: | Thesis Book |
| Language: | English |
| Published: |
2012 [erschienen] 2013
|
| Subjects: | |
| Online Access: | Volltext Inhaltsverzeichnis |
| Item Description: | Online erschienen: 2014, Zsfassung in dt. und engl. Sprache |
| Physical Description: | 164 Bl. Ill., graph. Darst., Kt. 30 cm |
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| 100 | 1 | |a Nono, Justin |d 1985- |e Verfasser |0 (DE-588)1059144212 |4 aut | |
| 245 | 1 | 0 | |a Immunomodulation through excretory-secretory products of the parasitic helminth Echinococcus multilocularis |c submitted by Justin Nono |
| 246 | 1 | 3 | |a Immunmodulation durch exkretorisch-sekretorischen Produkten der parasitaren Helminthen Echinococcus multilocularis |
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Record in the Search Index
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| adam_text | IMMUNOMODULATION THROUGH EXCRETORY/SECRETORY PRODUCTS OF THE
PARASITIC HELMINTH ECHINOCOCCUS MULTILOCULARIS
IMMUNMODULATION DURCH EXKRETORISCH/SEKRETORISCHEN PRODUKTEN DER
PARASITAREN HELMINTHEN
ECHINOCOCCUS MULTILOCULARIS
DOCTORAL THESIS FOR A DOCTORAL DEGREE
AT THE GRADUATE SCHOOL OF LIFE SCIENCES,
JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG,
SECTION INFECTION AND IMMUNITY
SUBMITTED BY
JUSTIN NONO
FROM
BAFOUSSAM, CAMEROON
WURZBURG 2012
HTTP://D-NB.INFO/105876649X
CONTENTS
ACKNOWLEDGEMENTS 7
SUMMARY 9
ZUSAMMENFASSUNG 11
1-INTRODUCTIO N 14
1.1 OVERVIEW OF HELMINTH INFECTIONS 14
1.2 THE
FOX-TAPEWORM ECHINOCOCCUS
MULTILOCULARIS 14
1.2.1 PHYTOGENY. 14
1.2.2 EPIDEMIOLOGY 16
1.2.3 LIFE CYCLE 17
1.2.4 CLINICAL MANIFESTATIONS OF AE. 20
1.2.5 PREVENTION AND CONTROL OF ALVEOLAR ECHINOCOCCOSIS 21
L .3 HOST IMMUNE RESPONSE
TO ECHINOCOCCUS MULTILOCULARIS 25
1.3.
1 THE HOST IMMUNE SYSTEM 25
1.3.2 IMMUNITY AND SUSCEPTIBILITY TO ECHINOCOCCUS MULTILOCULARIS 33
1.4 MAINTENANCE
OF E. MULTILOCULARIS LARVAE IN THE LABORATORY 36
1.5 OBJECTIVES 37
2-MATERIALS AND METHODS 38
2.1 MATERIAL 38
2.1.1 EQUIPMENT. 38
2.1.2 CONSUMABLES 39
2.1.3 CHEMICALS, MEDIA, COMMERCIALLY AVAILABLE KITS AND ENZYMES 40
2.1.4 ANTIBODIES 42
2.1.5 SOFTWARES, ONLINE BIOINFORMATICS TOOLS AND DATABASES 43
2.1.6 ANIMALS 43
2.2 EFFECTS OF E/S PRODUCTS OF ECHINOCOCCUS MULTILOCULARIS LARVAE ON
MURINE DC 44
2.2. /
ETHICS STATEMENT. 44
2.2.2 IN VIVO MAINTENANCE OF ECHINOCOCCUS MULTILOCULARIS LARVAL TISSUE.
44
2.2.3 IN VITRO CULTIVATION OFE. MULTILOCULARIS LARVAL TISSUE 45
2.2.4 PCR-BASED ASSESSMENT OF HOST CELL REMNANTS 47
2.2.5 NORMALIZATION OF ECHINOCOCCUS MULTILOCULARIS LARVAE BIOMASSES 47
2.2.6 PREPARATION OF ECHINOCOCCUS MULTILOCULARIS E/S PRODUCTS 48
2.2.7 GENERATION OF MURINE BONE MARROW-DERIVED DENDRITIC CELLS 49
2.2.8 ISOLATION OF MURINE SPLENOCYTES 49
2.2.9 HUMAN RED BLOOD CELLS PREPARATION
50
2.2.10 ASSESSMENT OF THE INFLUENCE OF ECHINOCOCCUS MULTILOCULARIS LARVAE
E/S PRODUCTS ON HOST CELLS
50
2.2.11 STATISTICAL ANALYSIS. 52
2.3. INFLUENCE
OF E/S PRODUCTS OF E. MULTILOCULARIS LARVAE ON FOXP3+
TREG EXPANSION 53
2.3.1 ETHICS STATEMENT
53
2.3.2 PARASITE MATERIAL 53
2.3.3 MICE 53
2.3.4 PERITONEAL LAVAGE 54
I
4
2.3.5 FLOW CYTOMETRIC ANALYSES
54
2.3.6 IN VITRO REGULATORY T-CELL SUPPRESSION ASSAY.
55
2.3.7 IN VITRO REGULATORY T-CELL CONVERSION ASSAY. 56
2.3.8 IN VITRO IL-IO SECRETION ASSAY 56
2.3.9 STATISTICAL ANALYSES
57
2.4.
E.
MULTILOCULAR1S LARVAE E/S PRODUCTS AND FOXP3+ TREGS 57
2.4.1 ANIMALS AND ETHICS STATEMENT.
57
2.4.2 PARASITE MATERIAL 58
2.4.3 ECHINOCOCCUS MULTILOCULARIS GENOME SEQUENCING PROJECT. 58
2.4.4 IDENTIFICATION OF PARASITE FACTORS, CLONING AND SEQUENCE ANALYSIS
58
2.4.5 RECOMBINANT EXPRESSION, PROTEIN PURIFICATION AND ANTISERUM
GENERATION 60
2.4.6 ASSESSMENT OF FACTOR SECRETION BY IN VITRO CULTIVATED METACESTODES
AND TRANSFECTED HEK CELLS 63
2.4.7 TREATMENT OF MURINE BMDC. 63
2.4.8 TREG CONVERSION ASSAY 64
2.4.9 IL-IO SECRETION ASSAY 64
2.4.10 STATISTICAL ANALYSES 65
2.5
E.
MULTILOCULARIS LARVAE E/S PRODUCTS AND TH1 IMMUNE RESPONSES 65
2.5.1 ANIMALS AND ETHICS STATEMENT. 65
2.5.2 PARASITE MATERIAL 65
2.5.3 IDENTIFICATION OF PARASITE FACTORS, CLONING AND SEQUENCE ANALYSIS
65
2.5.4 RECOMBINANT EXPRESSION OFEMTIP AND GENERATION OF ANTISERUM 68
2.5.5 EXPRESSION PROFILE OFEMTIP. 70
2.5.6 IMMUNOHISTOCHEMICAL LOCALIZATION OFEMTIP WITHIN ECHINOCOCCUS
MULTILOCULARIS LARVAE 71
2.5.7 NEUTRALIZATION OFEMTIP DURING ECHINOCOCCUS PRIMARY CELLS
CULTIVATION 72
2.5.8 IN VITRO STIMULATION OF CD4+ T-CELLS 73
2.5.9 STATISTICAL ANALYSES
74
3. RESULTS 75
3.1 ISOLATION AND NORMALIZATION OF
E.
MULTILOCULARIS LARVAL MATERIAL 75
3.2 EXCRETORY/SECRETORY-PRODUCTS
OF ECHINOCOCCUS MULTILOCULARIS LARVAE
INDUCE APOPTOSIS AND
TOLEROGENIC PROPERTIES IN
DENDRITIC CELLS IN VITRO 78
3.2.1 E/S PRODUCTS OFE. MULTILOCULARIS PRIMARY CELLS AND METACESTODES
BUT NOT THOSE OF PROTOSCOLECES KILL DC
IN VITRO 78
3.2.2 E/S PRODUCTS OFE. MULTILOCULARIS PRIMARY CELLS AND METACESTODES
INDUCE DC DEATH VIA APOPTOSIS 80
3.2.3 E/S PRODUCTS OFE. MULTILOCULARIS PRIMAY CELLS AND METACESTODES BUT
NOT THOSE OF PROTOSCOLECES IMPAIR
DC MATURATION AND RESPONSIVENESS IN VITRO 81
3.3 EXPANSION OF REGULATORY T-CELLS (TREG) BY
E.
MULTILOCULARIS
METACESTODES 84
3.3.1 E/S PRODUCTS OF E. MULTILOCULARIS METACESTODE VESICLES PROMOTE
FOXP3 EXPRESSION AND THE PRODUCTION OF
THE ANTI-INFLAMMATORY CYTOKINE IL-IO BY CD4+ T-CELLS IN VITRO 84
3.3.2 E. MULTILOCULARIS METACESTODES EXPAND BONA FIDE FOXP3+ REGULATORY
T-CELLS IN MICE 85
3.3.3 E. MULTILOCULARIS METACESTODES EXPAND REGULATORY T-CELLS THROUGH
THE HOST TGF-FI SIGNALING LOOP 91
3.4 AN ACTIVIN-ORTHOLOG SECRETED BY ECHINOCOCCUS
MULTILOCULARIS METACESTODES PROMOTES
REGULATORY T-CELL CONVERSION IN VITRO. 92
3.4.1 EMACT IS A TGF-FI SUPERFAMILY MEMBER SECRETED BY IN VITRO
CULTIVATED E. MULTILOCULARIS METACESTODES. 92
3.4.2 EMACT PROMOTES IL-IO PRODUCTION AND EXPRESSION OF THE MASTER
REGULATORY TRANSCRIPTION FACTOR FOXP3
IN CD4+ T-CELLS IN VITRO 93
I
5
3.5 EMTIP, A T-CELL
IMMUNOMODULATORY PROTEIN SECRETED BY
E. MULTILOCULARIS IS
IMPORTANT FOR
EARLY
LARVAL DEVELOPMENT 99
3.5.1 IDENTIFICATION OF EMTIP, A T-CELL IMMUNOMODULATORY PROTEIN
HOMOLOGUE FROM E. MULTILOCULARIS 99
3.5.2 EXPRESSION AND LOCALIZATION OF EMTIP DURING LARVAL DEVELOPMENT 102
3.5.3 EMTIP TRIGGERS I FN-Y SECRETION BY CD4+ T CELLS 105
3.5.4 ANTI-EMTIP ANTIBODIES BLOCK E. MULTILOCULARIS PRIMARY CELL
PROLIFERATION AND THE GENERATION OF
METACESTODE VESICLES 107
4. DISCUSSION 110
4.1 MODULATION OF THE HOST IMMUNE SYSTEM BY E. MULTILOCULARIS
LARVAE E/S PRODUCTS: LARVAE-SPECIFIC
EFFECTS ON HOST IMMUNE CELLS 110
4.2 UTILIZING EVOLUTIONARILY CONSERVED CYTOKINES TO
SUBVERT THE HOST IMMUNE RESPONSE:
EMACT, AN
ECHINOCOCCUS MULTILOCULARIS ACTIVIN THAT EXPANDS HOST REGULATORY T-CELLS
117
4.3 AN IFN-GAMMA-INDUCING PROTEIN SECRETED BY ECHINOCOCCUS
MULTILOCULARIS LARVAE IS
IMPORTANT
FOR PARASITE DEVELOPMENT 121
4.4 A MODEL FOR THE IMMUNOMODULATION OF HOSTS BY ECHINOCOCCUS
MULTILOCULARIS 125
5. BIBLIOGRAPHY 130
6. SUPPLEMENTARY FIGURES 154
7. LIST OF ABBREVIATIONS 160
8. PUBLICATIONS 162
8.1 ORIGINAL PUBLICATIONS 162
8.2. CONFERENCE
CONTRIBUTIONS 163
9. CURRICULUM VITAE 164
I
6
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| spelling | Nono, Justin 1985- Verfasser (DE-588)1059144212 aut Immunomodulation through excretory-secretory products of the parasitic helminth Echinococcus multilocularis submitted by Justin Nono Immunmodulation durch exkretorisch-sekretorischen Produkten der parasitaren Helminthen Echinococcus multilocularis 2012 [erschienen] 2013 164 Bl. Ill., graph. Darst., Kt. 30 cm txt rdacontent n rdamedia nc rdacarrier Online erschienen: 2014, Zsfassung in dt. und engl. Sprache Würzburg, Univ., Diss., 2013 Immunmodulation (DE-588)4315157-7 gnd rswk-swf Regulatorischer T-Lymphozyt (DE-588)1032038217 gnd rswk-swf Dendritische Zelle (DE-588)4313846-9 gnd rswk-swf Fuchsbandwurm (DE-588)4290099-2 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Fuchsbandwurm (DE-588)4290099-2 s Dendritische Zelle (DE-588)4313846-9 s Immunmodulation (DE-588)4315157-7 s Regulatorischer T-Lymphozyt (DE-588)1032038217 s DE-604 Erscheint auch als Online-Ausgabe urn:nbn:de:bvb:20-opus-85449 https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-85449 Resolving-System kostenfrei Volltext DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027655963&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Nono, Justin 1985- Immunomodulation through excretory-secretory products of the parasitic helminth Echinococcus multilocularis Immunmodulation (DE-588)4315157-7 gnd Regulatorischer T-Lymphozyt (DE-588)1032038217 gnd Dendritische Zelle (DE-588)4313846-9 gnd Fuchsbandwurm (DE-588)4290099-2 gnd |
| subject_GND | (DE-588)4315157-7 (DE-588)1032038217 (DE-588)4313846-9 (DE-588)4290099-2 (DE-588)4113937-9 |
| title | Immunomodulation through excretory-secretory products of the parasitic helminth Echinococcus multilocularis |
| title_alt | Immunmodulation durch exkretorisch-sekretorischen Produkten der parasitaren Helminthen Echinococcus multilocularis |
| title_auth | Immunomodulation through excretory-secretory products of the parasitic helminth Echinococcus multilocularis |
| title_exact_search | Immunomodulation through excretory-secretory products of the parasitic helminth Echinococcus multilocularis |
| title_full | Immunomodulation through excretory-secretory products of the parasitic helminth Echinococcus multilocularis submitted by Justin Nono |
| title_fullStr | Immunomodulation through excretory-secretory products of the parasitic helminth Echinococcus multilocularis submitted by Justin Nono |
| title_full_unstemmed | Immunomodulation through excretory-secretory products of the parasitic helminth Echinococcus multilocularis submitted by Justin Nono |
| title_short | Immunomodulation through excretory-secretory products of the parasitic helminth Echinococcus multilocularis |
| title_sort | immunomodulation through excretory secretory products of the parasitic helminth echinococcus multilocularis |
| topic | Immunmodulation (DE-588)4315157-7 gnd Regulatorischer T-Lymphozyt (DE-588)1032038217 gnd Dendritische Zelle (DE-588)4313846-9 gnd Fuchsbandwurm (DE-588)4290099-2 gnd |
| topic_facet | Immunmodulation Regulatorischer T-Lymphozyt Dendritische Zelle Fuchsbandwurm Hochschulschrift |
| url | https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-85449 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027655963&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT nonojustin immunomodulationthroughexcretorysecretoryproductsoftheparasitichelminthechinococcusmultilocularis AT nonojustin immunmodulationdurchexkretorischsekretorischenproduktenderparasitarenhelminthenechinococcusmultilocularis |