genomewide characterization of host-pathogen interactions by ...

More documents

Recommendations

Info

Maren Depke Results Gene Expression Pattern of Bone-Marrow Derived Macrophages after Interferon-gamma Treatment Table R.3.10: Global functional analysis of genes exhibiting strain differences in BMM of at least one treatment group, medium control or after IFN-γ treatment, using Ingenuity Pathway Analysis (Ingenuity Systems, www.ingenuity.com). Diseases and Disorders category p-value a of number genes Inflammatory Response Cancer Antimicrobial Response Inflammatory Disease Genetic Disorder Connective Tissue Disorders Skeletal and Muscular Disorders Gastrointestinal Disease Metabolic Disease Immunological Disease 1.51E-02 - 2.19E-14 1.51E-02 - 6.88E-14 5.60E-05 - 6.53E-11 1.51E-02 - 1.09E-10 1.51E-02 - 3.99E-08 1.51E-02 - 4.61E-08 1.51E-02 - 4.61E-08 1.51E-02 - 6.60E-07 1.51E-02 - 8.95E-07 1.51E-02 - 4.22E-06 69 Molecular and Cellular Functions category p-value a of number genes Cellular Growth and Proliferation 95 Lipid Metabolism 18 Small Molecule Biochemistry 88 Cell Death 146 Cellular Movement 58 78 Cell-To-Cell Signaling and Interaction Antigen Presentation 70 Cell Morphology a Ten categories with the smallest p-values are cited. D. a. F. – Development and Function 75 66 Cellular Development Carbohydrate Metabolism 1.36E-02 - 2.43E-08 1.51E-02 - 4.00E-08 1.51E-02 - 4.00E-08 8.68E-03 - 5.49E-07 1.51E-02 - 5.53E-07 1.51E-02 - 1.14E-06 1.19E-02 - 1.08E-05 1.51E-02 - 1.86E-05 1.51E-02 - 1.86E-05 1.51E-02 - 3.81E-05 92 28 42 81 47 64 24 38 44 Physiological System Development and Function category p-value a of number genes Hematological System D. a. F. Immune Cell Trafficking Cardiovascular System D. a. F. Organismal Development Humoral Immune Response Organismal Survival Cell-mediated Immune Response Tissue Development Tissue Morphology 20 Hematopoiesis 1.51E-02 - 7.63E-07 1.37E-02 - 7.63E-07 1.51E-02 - 3.45E-05 9.01E-03 - 3.45E-05 1.51E-02 - 5.60E-05 1.45E-02 - 6.36E-05 1.51E-02 - 7.36E-05 1.51E-02 - 1.43E-04 1.37E-02 - 2.29E-04 1.51E-02 - 7.48E-04 65 38 30 18 14 19 13 29 35 35 Table R.3.11: Canonical pathway analysis of genes exhibiting strain differences in BMM of at least one treatment group, medium control or after IFN-γ treatment, using Ingenuity Pathway Analysis (Ingenuity Systems, www.ingenuity.com). Pathway ratio a p-value Complement System 4/36 = 0,111 1,04E-03 Crosstalk between Dendritic Cells and Natural Killer Cells 8/98 = 0,082 1,45E-05 Role of Pattern Recognition Receptors in Recognition of Bacteria and Viruses 7/86 = 0,081 1,08E-04 Antigen Presentation Pathway 3/39 = 0,077 4,87E-03 Allograft Rejection Signaling 3/45 = 0,067 6,18E-03 Autoimmune Thyroid Diseases Signaling 3/47 = 0,064 7,69E-03 Caveolar-mediated Endocytosis Signaling 5/83 = 0,060 4,44E-03 Role of RIG1-like receptors in Antiviral Innate Immunity 3/52 = 0,058 1,34E-02 IL-10 Signaling 4/70 = 0,057 1,02E-02 Toll-like Receptor Signaling 3/54 = 0,056 3,06E-02 a Ten pathways with the highest ratio values which additionally are over-represented with p < 0.05 are cited. Manual data mining revealed different cytokines and cytokine receptors, which were differentially expressed between BMM of the two strain at control level, upon treatment with IFN-γ, or in both conditions (Table R.3.12). Certain chemotactic chemokines were higher expressed in BALB/c BMM (Ccl24, Cxcl11, Cxcl14), but also for the receptor Ccr2, which binds Ccl2, Ccl7, and Ccl13 chemokines, and Cxcr4, whose ligand is Cxcl12, higher expression was observed in BALB/c BMM. Additionally, IL-15, a 104
Maren Depke Results Gene Expression Pattern of Bone-Marrow Derived Macrophages after Interferon-gamma Treatment regulatory, anti-apoptotic cytokine with structural similarity to IL-2, and the immune modulators Tnfsf8 and Tnfsf18, members of the TNF ligand superfamily, were higher expressed in BALB/c BMM. Strain differences were observed for the interleukin receptors Il4ra (alpha-chain of IL-4 receptor), Il13ra1 (primary IL-13 binding subunit of the IL-13 receptor), and Il21r (IL-21 receptor). Il4ra and Il13ra1 are linked, because Il13ra1 builds a receptor complex together with Il4ra. All three interleukin receptor chains were higher expressed in C57BL/6 BMM (Table R.3.12). Table R.3.12: Strain differences in gene expression of cytokines and cytokine receptors between BMM of BALB/c and C57BL/6 mice. Rosetta Resolver Annotation fold change a IFN-γ effect gene Entrez description alias name Gene ID control IFN-γ BALB/c C57BL/6 Ccl24 chemokine (C-C motif) ligand 24 CKb-6, MPIF-2, Scya24 56221 -2.7 -2.2 Ccr2 chemokine (C-C motif) receptor 2 Ckr2, Ccr2a, Ccr2b, Ckr2a, Ckr2b, mJe-r, 12772 -2.8 -4.0 Cmkbr2, Cc-ckr-2 Cxcl11 chemokine (C-X-C motif) ligand 11 IP9, H174, ITAC, b-R1, CXC11, I-TAC, SCYB9B, 56066 -1.0 -7.6 x Scyb11, betaR1 Cxcl14 chemokine (C-X-C motif) ligand 14 KS1, Kec, BMAC, BRAK, NJAC, MIP-2g, Scyb14, 57266 -4.0 -6.1 bolekine, MIP2gamma Cxcr4 chemokine (C-X-C motif) receptor 4 CD184, LESTR, Sdf1r, Cmkar4, PB-CKR, 12767 -2.1 -2.5 x PBSF/SDF-1 Il4ra interleukin 4 receptor, alpha Il4r, CD124 16190 2.2 1.7 x x Il13ra1 interleukin 13 receptor, alpha 1 NR4, Il13ra, CD213a1 16164 1.7 1.4 x x Il15 interleukin 15 16168 -1.5 -2.0 x Il21r interleukin 21 receptor NILR 60504 3.3 2.8 x Tnfsf18 tumor necrosis factor (ligand) superfamily, member 18 Gitrl 240873 1.0 -3.0 x Tnfsf8 tumor necrosis factor (ligand) superfamily, member 8 CD153, Cd30l, CD30LG 21949 -1.8 -5.2 a Fold change values were calculated for the comparison of C57BL/6 BMM with the baseline of BALB/c BMM of mean values from three biological replicates per group. Positive values indicate higher expression in C57BL/6 BMM than in BALB/c BMM, whereas negative values indicate higher expression in BALB/c BMM than in C57BL/6 BMM. Differential expression between BMM of the two strains at the same treatment level (IFN-γ treated or medium control) using statistical testing in combination with an absolute fold change cutoff of 1.5 is indicated in bold. Furthermore, four GTPases / GTP binding proteins of the p65 and the Mx families, which were already observed to be induced by IFN-γ within the data set of BALB/c and C57BL/6 BMM, exhibited strain differences. Gbp1, Mx1, and Mx2 were higher expressed in BALB/c BMM, whereas Gbp2 was higher expressed in C57BL/6 BMM. Complement system components C1qb and C1qc, the receptor for complement factor fragment C5a, C5ar1, but also the complement factor C1 inhibitor, Serping1, were higher expressed in C57BL/6 BMM (Table R.3.13). Other immune function related gene expression differences between BMM of the two strains were conspicuous, because the genes were clearly affected by IFN-γ treatment. First, MHC genes of class I (H28, H2-Q6, H2-Q8, H2-T24) and class II (H2-Ea) were higher expressed in BALB/c BMM. But also H2-Ab1 (class II), H2-K1, and H2-M2 (class I) exhibited strain differences, however, their expression was higher in C57BL/6 BMM. Second, a group of interferon-inducible genes possessed differences in their expression between BMM of both strains: Ifi27l2a, Ifi44, Ifi202, Ifi203, Ifih1, Ifit3, Ifitm3, Irf7, and Isg20. All of them were higher expressed in BALB/c BMM than in C57BL/6 BMM (Table R.3.14). 105
Page 1 and 2:
G E N O M E W I D E C H A R A C T E
Page 3 and 4:
Maren Depke C O N T E N T S GENOMEW
Page 5 and 6:
Maren Depke Z U S A M M E N F A S S
Page 7 and 8:
Maren Depke Zusammenfassung der Dis
Page 9 and 10:
Maren Depke S U M M A R Y O F D I S
Page 11 and 12:
Maren Depke Summary of Dissertation
Page 13 and 14:
Maren Depke I N T R O D U C T I O N
Page 15 and 16:
Maren Depke Introduction Besides op
Page 17 and 18:
Maren Depke Introduction Extracellu
Page 19 and 20:
Maren Depke Introduction with heigh
Page 21 and 22:
Maren Depke Introduction 2005). SaP
Page 23 and 24:
Maren Depke Introduction contains a
Page 25 and 26:
Maren Depke Introduction via fibron
Page 27 and 28:
Maren Depke Introduction cathelicid
Page 29 and 30:
Maren Depke Introduction shock are
Page 31 and 32:
Maren Depke Introduction STUDIES OF
Page 33 and 34:
Maren Depke Introduction are effect
Page 35 and 36:
Maren Depke Introduction cell stimu
Page 37 and 38:
Maren Depke Introduction channel CF
Page 39 and 40:
Maren Depke M A T E R I A L A N D M
Page 41:
Maren Depke Material and Methods Li
Page 44 and 45:
Maren Depke Material and Methods Ki
Page 47 and 48:
Maren Depke Material and Methods GE
Page 49:
Maren Depke Material and Methods Ge
Page 52 and 53:
Maren Depke Material and Methods Ho
Page 54 and 55: Maren Depke Material and Methods Ho
Page 56 and 57: Maren Depke Material and Methods Pa
Page 63 and 64: corticosterone [pg/ml plasma] corti
Page 65 and 66: Maren Depke Results Liver Gene Expr
Page 67 and 68: lood glucose levels [nmol/l] resist
Page 69 and 70: LBP [ng/ml] CPR [ng/ml] Maren Depke
Page 71 and 72: Maren Depke Results Liver Gene Expr
Page 73 and 74: liver weight [g] Maren Depke Result
Page 75 and 76: infection rate cfu / 10 mg tissue c
Page 77 and 78: Maren Depke Results Kidney Gene Exp
Page 79 and 80: Table R.2.1: Genes displaying stati
Page 81 and 82: Maren Depke BR1 sign DsigB vs wt BR
Page 91 and 92: Maren Depke Results GENE EXPRESSION
Page 93 and 94: Maren Depke Results Gene Expression
Page 95 and 96: log2(ratio C57BL/6 / BALB/c) at IFN
Page 103: Maren Depke Results Gene Expression
Page 109: Maren Depke Results Gene Expression
Page 112 and 113: Maren Depke Results Host Cell Gene
Page 132 and 133: Maren Depke Results Pathogen Gene E
Page 138 and 139: S. aureus RN1HG sample conditions a
Page 148 and 149: mean normalized intensity mean norm
Page 154 and 155:
mean normalized intensity mean norm
Page 156 and 157:
Maren Depke Results Pathogen Gene E
Page 158 and 159:
mean normalized intensity Maren Dep
Page 160 and 161:
Maren Depke Results Pathogen Gene E
Page 162 and 163:
Page 164 and 165:
Page 166 and 167:
Page 168 and 169:
log 2 (ratio) log 2 (ratio) log 2 (
Page 171 and 172:
Maren Depke D I S C U S S I O N A N
Page 173 and 174:
Maren Depke Discussion and Conclusi
Page 175 and 176:
Page 177 and 178:
Page 179 and 180:
Page 181 and 182:
Page 183 and 184:
Page 185 and 186:
Page 187 and 188:
Page 189 and 190:
Page 191 and 192:
Page 193 and 194:
Page 195 and 196:
Page 197 and 198:
Page 199 and 200:
Page 201 and 202:
Page 203 and 204:
Page 205:
Page 208 and 209:
Maren Depke References Athanasopoul
Page 210 and 211:
Maren Depke References Byrne GI, Le
Page 212 and 213:
Maren Depke References Demling R. T
Page 214 and 215:
Maren Depke References Foss GS, Pry
Page 216 and 217:
Maren Depke References Hagopian K,
Page 218 and 219:
Maren Depke References Jin T, Bokar
Page 220 and 221:
Maren Depke References Kwan T, Liu
Page 222 and 223:
Maren Depke References Luster AD, U
Page 224 and 225:
Maren Depke References Namiki S, Na
Page 226 and 227:
Maren Depke References Puccetti P.
Page 228 and 229:
Maren Depke References Siewert E, B
Page 230 and 231:
Maren Depke References van den Akke
Page 232 and 233:
Maren Depke References Yang XL, Sch
Page 235:
Maren Depke A F F I D A V I T / E R
Page 238 and 239:
Maren Depke Acknowledgments Kidney
show all

genomewide characterization of host-pathogen interactions by ...

Create successful ePaper yourself

Delete template?

Save as template?