Polymorphism in the IRG resistance system determines virulence of Toxoplasma gondii in mice:
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| Format: | Thesis Book |
| Language: | English |
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2015
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| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Item Description: | Zsfassung in dt. und engl. Sprache |
| Physical Description: | 165 S. Ill., graph. Darst. CD-ROM (12 cm) |
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| adam_text | Titel: Polymorphism in the IRG resistance system determines virulence of Toxoplasma gondii in mice
Autor: Müller, Urs Benedikt
Jahr: 2015
Table of Contents
1. Introduction................................................................................................................1
1.1. Species interactions as driving force for evolution.............................................1
1.2. Parasitism and host defense.................................................................................2
1.3. Toxoplasma gondii..............................................................................................5
1.3.1. The sexual cycle...........................................................................................6
1.3.2. The asexual cycle.........................................................................................7
1.3.3. Population structure of T. gondii..................................................................9
1.3.4. T. gondii: immune sensing and immune responses....................................10
1.4. Interferon-inducible GTPases............................................................................15
1.5. Immunity-related GTPases................................................................................15
1.5.1. IRG protein-mediated cell-autonomous resistance against T. gondii.........18
1.5.2. Inactivation of the IRG resistance system by virulent T. gondii................20
1.5.3. In vitro resistance to virulent T. gondii......................................................22
1.6. Radiation of the house mouse Mus musculus....................................................24
1.7. The aim of this study.........................................................................................26
2. Material and Methods...............................................................................................28
2.1. Material..............................................................................................................28
2.1.1. Chemicals, solutions and buffers................................................................28
2.1.2. Enzymes and proteins.................................................................................29
2.1.3. Kits.............................................................................................................30
2.1.4. Media for cell culture.................................................................................30
2.1.5. Immunoreagents.........................................................................................30
2.1.6. Mice............................................................................................................31
2.1.7. Rational for Mus musculus sample locations.............................................34
2.1.8. Oligonucleotides.........................................................................................35
2.1.9. T. gondii strains..........................................................................................36
2.2. In vivo infections with T. gondii........................................................................36
2.2.1. Mouse survival assays................................................................................36
2.2.2. Quantitation of T. gondii cysts in brains of infected mice.........................36
2.2.3. Flow cytometry to assay infected peritoneal cells......................................36
2.3. Cell Biology.......................................................................................................37
2.3.1. Preparation of tissue culture lines from mouse diaphragm cells................37
2.3.2. Preparation of bone-marrow derived macrophages....................................38
2.3.3. Culture of T. gondii strains.........................................................................38
2.3.4. T. gondii proliferation assay.......................................................................38
2.3.5. Immunofluorescence microscopy and analysis..........................................39
2.4. Molecular Biology.............................................................................................40
2.4.1. Isolation of genomic DNA from mouse tissue samples.............................40
2.4.2. Sequencing PCR of mitochondrial D-loop.................................................40
2.4.3. Preparation of total RNA for Illumina transcriptome sequencing..............41
2.4.4. PCR protocols and agarose gel electrophoresis..........................................41
2.4.5. Restriction digest........................................................................................42
2.4.6. Generation of cell lysates for SDS-PAGE..................................................43
2.4.7. SDS-polyacrylamide gel electrophoresis (SDS-PAGE).............................43
2.4.8. Western blot analysis..................................................................................43
2.4.9. Determination of total protein concentration in cell lysates.......................44
2.5. Bioinformatics...................................................................................................44
3. Results I - Resistance of CIM mice to T. gondii and mapping of resistance...........45
3.1. Resistance of CIM mice against T. gondii.........................................................45
3.2. IRG-mediated resistance of CIM mice to virulent type I strains of T. gondii... 51
3.2.1. Resistance of (BL/6xClM)Fi hybrid mouse cell lines against virulent
T. gondii.....................................................................................................51
3.2.2. Expression of IRG allelic products in cell lines of (BL/6xCIM)Fi
hybrid mice.................................................................................................52
3.2.3. IRG-mediated resistance to virulent T. gondii in cells of
(BL/6xCIM)F 1 xBL/6 BCi mice.................................................................55
3.2.4. IRG-mediated resistance of BCi and F2 mice to virulent T. gondii...........61
4. Results n - Polymorphism in the IRG resistance system and
CIM resistance against South American T. gondii strains.....................65
4.1. Maternal phylogeny of wild and wild-derived Mus musculus..........................66
4.2. IRG protein polymorphism and cell-autonomous resistance............................68
4.2.1. IRG protein polymorphism.........................................................................68
4.2.2. IRG protein expression in cells of laboratory, wild and wild-derived
inbred Mus musculus..................................................................................71
4.2.3. Resistance of cells of wild and wild-derived mice against
virulent T. gondii........................................................................................73
4.2.4. Effects of cell density and IFNy-concentration on cellular resistance
against T. gondii.........................................................................................75
4.2.5. Independent contribution of M m. musculus IRG proteins from
chromosome 11 or 18 to cellular resistance against vimlent T. gondii......76
4.3. Characterization of CIM resistance against South American T. gondii............78
4.3.1. In vivo resistance to South American T. gondii..........................................78
4.3.2. Resistance of CIM and BEL-8 DDCs to South American T. gondii..........79
4.3.3. Resistance of CIM macrophages to South American T. gondii.................81
4.3.4. IRG expression level differences between IFNy-stimulated DDCs
and BMMs..................................................................................................83
5. Discussion.................................................................................................................86
5.1. Virulent T. gondii inactivate the IRG resistance system in laboratory mice.....87
5.2. Reciprocal virulence and resistance polymorphism between T. gondii and
Mus musculus....................................................................................................89
5.2.1. Resistance of the wild-derived inbred CIM mouse strain is mediated
via IRG proteins encoded on chromosome 11..........................................91
5.2.2. A possible function of chromosome 11 CIM IRG proteins.......................92
5.2.3. The role of the NLRP inflammasome sensors............................................94
5.3. Mus musculus and T. gondii in South American...............................................95
5.3.1. The CIM mouse strain from South India is not adapted to highly
virulent T. gondii strains from South America...........................................95
5.3.2. Origin of Mus musculus in Brazil...............................................................96
5.3.3. Domesticus-like mice from Brazil share musculus-like IRG
tandem proteins..........................................................................................98
5.3.4. Selection pressure on IRG proteins by T. gondii in South America..........99
5.4. Expression of IRG tandem proteins does not always correlate with
cellular resistance against virulent T. gondii...................................................102
5.5. IRG polymorphism driven by other mouse pathogens....................................103
5.6. IRG tandem proteins: another function in search of another mechanism.......104
5.7. IRG proteins are not the only resistance factors against T. gondii..................105
5.8. Irgml - never change a dangerous system......................................................106
5.9. Outlook............................................................................................................107
6. References..............................................................................................................109
7. Summary.................................................................................................................133
8. Zusammenfassung..................................................................................................134
9. Appendix................................................................................................................136
9.1. Nlrpl primer specificity..................................................................................136
9.2. Alignment of mitochondrial D-loop sequences...............................................137
9.3. Mouse sample sites and geographic origin of wild-derived inbred mice........159
9.4. Standart curve for determination of protein concentrations............................160
10. Collaborations.......................................................................................................161
11. Acknowledgements..............................................................................................162
12. Erklärung..............................................................................................................164
13. Lebenslauf............................................................................................................165
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| author | Müller, Urs Benedikt 1981- |
| author_GND | (DE-588)1071924621 |
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| dewey-tens | 570 - Biology |
| discipline | Biologie |
| format | Thesis Book |
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| spelling | Müller, Urs Benedikt 1981- Verfasser (DE-588)1071924621 aut Polymorphism in the IRG resistance system determines virulence of Toxoplasma gondii in mice vorgelegt von Urs Benedikt Müller 2015 165 S. Ill., graph. Darst. CD-ROM (12 cm) txt rdacontent n rdamedia nc rdacarrier Zsfassung in dt. und engl. Sprache Köln, Univ., Diss., 2014 (DE-588)4113937-9 Hochschulschrift gnd-content HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=028205422&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Müller, Urs Benedikt 1981- Polymorphism in the IRG resistance system determines virulence of Toxoplasma gondii in mice |
| subject_GND | (DE-588)4113937-9 |
| title | Polymorphism in the IRG resistance system determines virulence of Toxoplasma gondii in mice |
| title_auth | Polymorphism in the IRG resistance system determines virulence of Toxoplasma gondii in mice |
| title_exact_search | Polymorphism in the IRG resistance system determines virulence of Toxoplasma gondii in mice |
| title_full | Polymorphism in the IRG resistance system determines virulence of Toxoplasma gondii in mice vorgelegt von Urs Benedikt Müller |
| title_fullStr | Polymorphism in the IRG resistance system determines virulence of Toxoplasma gondii in mice vorgelegt von Urs Benedikt Müller |
| title_full_unstemmed | Polymorphism in the IRG resistance system determines virulence of Toxoplasma gondii in mice vorgelegt von Urs Benedikt Müller |
| title_short | Polymorphism in the IRG resistance system determines virulence of Toxoplasma gondii in mice |
| title_sort | polymorphism in the irg resistance system determines virulence of toxoplasma gondii in mice |
| topic_facet | Hochschulschrift |
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