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8 on an IFN-
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13 1. Streptococcus pneumoniae Haemophilus Moraxella catarrhalis Staphylococcus aureus
14 Chapter Microbiota Virus Lumen IgG MAMPs IgA Mucus layer Periciliary layer Epithelial cells Local training of immune cells Lamina propria Viral replication Inflammatory mediators Reduced/enhanced viral pathogenesis Systemic training of immune cells Vein 12
15 Maternal IgG Peak severe RSV infections Colonization 1 Antiviral response Own IgG Th1 cytokines Anti-inflammatory Th2 cytokines Th17 cytokines 3 mo 6 mo 9 mo Birth 1 yr 2 yrs in utero ).. de novo )
16 Chapter in vitro. In in vitro. 14
17 II 6 in vitro Streptococcus pneumoniae in vivo S. pneumoniae 1 15
18 Chapter 1 1 et al et al. et al. et al. et al. et al. 20. et al. et al. et al. et al.
19 et al. et al. et al. et al. et al. et al. et al. 1 17
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22 Chapter 2 2 in vitro 20
23 An in vitro 1. A 2. in vitro. 5 in vivo in 2 21
24 Chapter 2 vitro 2 22
25 An in vitro
26 Chapter
27 An in vitro PBS. 25
28 Chapter * A 7
29 An in vitro
30 Chapter A RPMI RSV A B C D RPMI MDP LPS Negative Control Negative Control Control Condition Control Condition Condition Control Condition Control Condition Control Condition Experimental Condition Experimental Condition Control Condition Experimental Condition Experimental Condition 28
31 An in vitro RSV infection (%) Monocytes NK cells CD4+ T cells MOI 0.2 MOI 1 MOI 5 CD8+ T cells TNF (fold change) IFN-y (fold change) RSV MDP RSV+MDP LPS 0 RSV MDP RSV+MDP LPS 29
32 Chapter 2 2 Candida albicans TNF (pg/ml) IFN-y (pg/ml) RPMI RSV MDP RSV+MDP LPS RPMI RSV MDP RSV+MDP LPS TNFα (pg/ml) IFNγ (pg/ml) RPMI RSV RSV-BPL RPMI RSV RSV-BPL
33 An in vitro et al
34 Chapter 2 2 in vivo 5 in vitro in vivo in vivo 17.
35 An in vitro et al. et al. et al. et al
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40 Chapter 3 3
41 1 3 Streptococcus Listeria monocytogenestoxoplasma gondii 4. 5
42 Chapter 3 3 a a a )
43 20. in vitro
44 Chapter )
45 LYN B cell Innate immune cell IgG-IC C1q C5a C5a C5b C5 C3b BCR ITIM SHIP FcγRIIB SHIP ITIM FcγRIIB C5aR ITAM ITAM ITAM ITAM SYK SYK SYK SYK FcγRI FcγRIIA FcγRIIC FcγRIII MyD88 TLR-4 3 RAS ERK RAS APOPTOSIS CELL INHIBITION CELL ACTIVATION. in vitro 54
46 Chapter 3 3 a a in vitro
47
48 Chapter
49 T. gondii Candida albicans et al. 47
50 Chapter 3 3. Streptococcus pneumoniae L. monocytogenes
51 MONOCYTES, DENDRITIC CELLS AND MACROPHAGES NK CELLS NEUTROPHILS, EOSINOPHILS, B CELLS COMPLEMENT MAST CELLS AND BASOPHILS SYSTEM Neutralizing IgG Enhancing IgG IgG IgG IgG IgG RSV RSV RSV RSV RSV Ig-IC 3 ITAM SYK SHIP ITIM ITAM SYK SHIP ITIM ITAM SYK SHIP ITIM SHIP ITIM C5a C1q C3b Activating FcγR Inhibitory FcγR Activating FcγR Inhibitory FcγR Activating FcγR Inhibitory FcγR Inhibitory FcγR C5b C5 NEUTRALIZATION ENHANCEMENT INCREASED CD56/FCYRIII NK CELLS ADCC INCREASED CYTOKINE RELEASE ACTIVATION OF NEUTROPHILS REDUCED SOMATIC HYPERMUTATION INCREASE IN CD4+ T CELLS
52 Chapter et al ). 50
53 In vitro in vitro in vivo 3 51
54 Chapter 3 3 et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. 52
55 et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. 3
56 Chapter 3 3 et al. et al. et al. et al. et al. et al. et al. 54
57 et al. et al. et al. et al. et al. 3 55
58 Chapter 3 3 et al. et al. et al.
59 et al. et al. et al. et al. et al. et al. et al. et al. 3 57
60 Chapter 3 3 et al. et al. et al. et al. 58
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64 Chapter 4 4
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66 Chapter
67 Microarray
68 Chapter 4 4 ). A Upregulated by inactivated RSV C2 SIGLEC1 USP18 RP1-93H18.5 INDO BCL2L14 G1P2 IFI44L FFAR2 IFIT2 GJB2 CCL7 BATF2 IFIT3 ETV7 APOBEC3A CXCL9 ANKRD22 RSAD2 TNFAIP6 SERPING1 IFIT1 IFI27 CXCL11 CXCL Fold change B Upregulated by inactivated RSV + HS OTOF SIGLEC1 SAMD4A CCL19 IFIT1 IFIT2 KIAA1199 ETV7 BCL2L14 ARNT2 G1P2 CCL7 LINCR APOBEC3A SERPING1 MDK BATF2 FFAR2 RSAD2 HES4 P8 CXCL10 DEFB1 IFI27 CXCL Fold change C Upregulated by antibodies CSAG1 CBR3 LINCR IFNA7 RETN IFNA10 IFNA17 IFNA14 PLEKHN1 S100A2 CYP19A1 IFNA8 IFNA5 CKB IFNA6 IFNA16 IFNA21 HES4 IFNA4 IFNA13 KIAA1199 IFNA2 CXCL11 IFNA1 DEFB Fold change - A - HS
69 A CXCL10 (pg/ml) * * * * * B CXCL11 (pg/ml) 800 * * * * Medium HS Ig - HS C IFNα (pg/ml) Medium RSV * * * Inactivated RSV * * D IFNγ (pg/ml) Medium RSV * * * Inactivated RSV * * 4 0 Medium RSV Inactivated RSV 0 Medium RSV Inactivated RSV - A D -
70 Chapter 4 4 A IFNα (pg/ml) CXCL10 (pg/ml) C Medium * RSV * B CXCL11 (pg/ml) D IFNγ (pg/ml) Medium RSV Medium HS Ig - HS 0 Medium RSV 0 Medium RSV - A D ). -
71 4 A CXCL10 (MFI) * B CXCL10 (pg/ml) * Medium RSV * * * * C CXCL10 (pg/ml) Medium HS * * 0 Monocytes NK cells B cells CD4+ T cells CD8+ T cells 0 Medium 2% 5% 10% 20% Pal HS 0 Medium MOI 0.2 MOI 1 MOI 5 C. A RSV
72 Chapter
73 4 71
74 72 Chapter 4 4
75 4 42..
76 Chapter 4 4 ** 4 RSV infection (%) * 0 Medium 2% 5% 10% 20% Ig- HS Pal HS - Fold increase CXCL10 (MFI) * Medium * HS Medium RSV 74
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80 Chapter
81 5 79
82 Chapter 5 A B C D Nasal IgG (AU) Viral load (Ct value) Viral load (Ct value) Nasal CXCL10 (pg/ml) p = r = Plasma IgG (AU) p = r = Plasma IgG (AU) p = r = Plasma CXCL10 (pg/ml) p = r = Plasma IgG (AU) Viral load (Ct value) Viral load (Ct value) Nasal CXCL10 (pg/ml) p = r = Nasal IgG (AU) p = r = Nasal CXCL10 (pg/ml) p = r = Nasal IgG (AU) A D). 80
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84 Chapter
85 5
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90 Chapter 6 6 Streptococcus pneumoniae Streptococcus pneumoniae Streptococcus pneumoniae Streptococcus pneumoniae 88
91 Streptococcus pneumoniae Streptococcus pneumoniae S. pneumoniae. S. pneumoniae S. pneumoniae 4 S. pneumoniae S. pneumoniae 5 S. pneumoniae S. pneumoniae S. pneumoniae S. pneumoniae S. pneumoniae 7 S. pneumoniae S. pneumoniae 6 89
92 Chapter 6 6 Streptococcus pneumoniae Moraxella catarrhalis 8 5 a 100 Streptococcus pneumoniae Staphylococcus aureus Moraxella catarrhalis S. aureusescherichia coli E. coli E. 90
93 Streptococcus pneumoniae coli 6 91
94 Chapter 6 Streptococcus pneumoniae Staphylococcus aureus Moraxella catarrhalis Haemophilus ). Moraxella catarrhalis. 6 A MMP-9 (pg/ml) p=0.06 p=0.06 B IL-1 β (pg/ml) * * 0 Medium SP SA MC HI Gram+ * * 0 Medium SP SA MC HI Gram- Gram+ Gram- Streptococcus pneumoniae Staphylococcus aureus Moraxella catarrhalis A E. coli 92
95 Streptococcus pneumoniae ). In A MMP-9 (pg/ml) Medium P3C (TLR1/2) * * p= 0.06 PGN-SA (TLR2) PGN-EB (TLR2) LTA (TLR2/6) LPS (TLR4) Flagellin (TLR5) CpG (TLR9) DNA E. coli (TLR9) * * * * * Tri-DAP (NOD1) mtri-dap (NOD1/2) MDP (NOD2) mtri-lys (NOD2) IL-1β (pg/ml) Medium * * P3C (TLR1/2) PGN-SA (TLR2) * * * PGN-EB (TLR2) LTA (TLR2/6) LPS (TLR4) * * Flagellin (TLR5) CpG (TLR9) DNA E. coli (TLR9) * * * mtri-lys (NOD2) Tri-DAP (NOD1) mtri-dap (NOD1/2) MDP (NOD2) E. coli A B 6 9
96 Chapter 6 A Controls NOD2fs *** MMP-9 (pg/ml) * B Medium LTA LPS MDP MDP+LPS ** ** 6 MMP-9 (pg/ml) ** ** Medium Live SP Bead-beaten HK SP HK MC HK HI SP A Streptococcus pneumoniae Streptococcus pneumoniaestreptococcus pneumoniae Moraxella catarrhalis S. pneumoniae 94
97 Streptococcus pneumoniae S. pneumoniae S. pneumoniae S. pneumoniae S. pneumoniaem. catarrhalis Streptococcus pneumoniae MMP-9 (fold change) 30 Controls NOD2fs * 6 0 MDP LPS MDP+LPS ). 95
98 Chapter 6 ). 6 A TIMP-1 (pg/ml) p = 0.06 * p = 0.06 B TIMP-1 (pg/ml) * 0 Medium LPS MDP MDP+LPS 0 Medium SP SA MC HI Gram+ Gram- Streptococcus pneumoniae Staphylococcus aureus Moraxella catarrhalis
99 Streptococcus pneumoniae S. pneumoniae S. pneumoniaes. pneumoniae 15 S. pneumoniae 17 S. pneumoniae S. pneumoniaes. pneumoniae S. pneumoniae S. pneumoniaes. pneumoniae S. pneumoniae 6 97
100 Chapter S. pneumoniae et al.s. pneumoniae 7 S. pneumoniae S. pneumoniae 98
101 Streptococcus pneumoniae S. pneumoniae 6 99
102 100 Chapter
103 101 Streptococcus pneumoniae
104 Chapter
105 Streptococcus pneumoniae A B MMP-9 (pg/ml) MMP-9 (pg/ml) Medium Medium µg/ml MDP µg/ml LPS A 6 A MMP-9 (pg/ml) ** ** * p=0.06 p=0.06 B MMP-9 (fold change) 30 Controls Crohn NOD2fs ** * 0 Medium MDP LPS MDP+LPS 0 MDP LPS MDP+LPS A
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108 Chapter 7 7
109 Orthomyxoviridae 1. In 2. 5 et al. et al
110 Chapter
111 E.coli
112 Chapter
113 19 C
114 Chapter in vitro
115 10 12 A. B. IAV-infected cells (%) Mock P3 C LTA PolyI:C LPS Flagellin CpG MDP C. D. HKx31-infected cells (%) * * *** *** ** Mock LPS Uninfected *** Virus-Infected cells (%) RSV-infected cells (%) Mock P3C LTA PolyI:C LPS Flagellin CpG MDP LPS PolyI:C 24 Time of pre-incubation (h) A D 7
116 Chapter ). 114
117 *** *** ). A. B. C. Adherence (%) μg IAV 0.88μg IAV Uninfected LPS Mock Surface binding (%) LPS Mock Incubation time (min) 60 Mock + Mock LPS + Mock IAV + Mock LPS + IAV Copy number (vrna) Mock + Mock LPS + Mock IAV + Mock LPS + IAV A Copy number (mrna)1500 * *** * * 7 115
118 Chapter 7 7 A. Pam3Cys PolyI:C LPS D. Fold change Medium LPS PolyI:C Pam3Cys 1 IFNβ IFNу RIG-I TNFα IFIT1 B. C. Immune effector process Response to biotic stimulus Immune effector process Response to biotic stimulus Response to virus Cytokine-mediated signaling pathway Interferon-gamma-mediated signaling pathway Negative regulation of viral genome replication Type I interferon-mediated signaling pathway Cytokine-mediated signaling pathway JAK-STAT cascade Interferon-gamma-mediated signaling pathway Response to virus Negative regulation of viral genome replication Type I interferon-mediated signaling pathway Ratio A D
119 in vitro 7 117
120 Chapter 7 A. Infectious virusparticles/ml B LPS Mock 16 Incubation time (hr) 24 C. Mock + IAV LPS + IAV LPS+Mock Mock+Mock Mock + Mock LPS+ Mock LPS+ IAV Mock + IAV CD107a + CD8 + cells (%) ** *** *** *** *** 7 CD107a 11.6% 11.8% 24.5% 28.5% 4.65% 5.64% 7.14% 9.17% IFN-γ FSC-A A 118
121 Streptococcus Moraxella catarrhalis
122 Chapter 7 7. in vivo et al
123 in vivo 7 121
124 122 Chapter
125 7
126 Chapter 7 A. B IAV-infected cells (%) Mock P3 C LTA PolyI:C LPS Flagellin CpG MDP *** *** RSV-infected cells (%) Mock P3C LTA PolyI:C LPS Flagellin CpG MDP A 124
127 A B. 500 IL-6 (pg/ml) C RPMI Pam3Cys LTA PolyI:C LPS Flagellin CpG MDP IL-10 (pg/ml) RPMI Pam3Cys LTA PolyI:C LPS Flagellin CpG MDP TNFα (pg/ml) RPMI Pam3Cys LTA PolyI:C LPS Flagellin CpG MDP A 7 A. B. Mock + Mock + IP Mock + Mock + IP CD107α 1.49% IFNγ 1.20% FSC-A FSC-A A 125
128 Chapter 7 Name CCL IFI44L IFI IFIH
129 7 127
130 Chapter 7 Name CCL SP CASP CFB
131 SLC25A CCL
132
133
134 Chapter 8 8
135 et al. 1 Paramyxoviridae
136 Chapter 8 8
137 E. coli 48 8
138 Chapter 8 8
139 cytokines IL-10 TNF-α IL-1β * 8 Ratio LTA + RSV LPS + RSV Flagellin + RSV CpG + RSV MDP + RSV
140 Chapter 8 A TNF-α (pg/ml) B IL-1β (pg/ml) Healthy controls NOD2fs RSV MDP Healthy controls NOD2fs * RSV+MDP *** LPS Ratio IL-1β Ratio TNF-α ** * Controls NOD2fs ** * 8 0 RSV MDP RSV+MDP A LPS 0 Controls NOD2fs 19
141 * TNF-α IL-1β Ratio * Poly(I:C) HMW + MDP Poly(I:C)-LyoVec LMW + MDP Poly(I:C)-LyoVec HMW + MDP * ssrna40-lyovec + MDP * LPS + MDP * R848 + MDP
142 Chapter 8 A Fold change h * * B Fold change h * * * 0.1 RSV MDP RSV + MDP LPS HMW Poly(I:C)-LyoVec LMW A 0.1 RSV MDP RSV + MDP LPS HMW Poly(I:C)-LyoVec LMW
143 A Fold change * TLR3 RIG-I * * * * * * * * * * B Fold change * NOD2 * * * 0.1 RSV MDP RSV + MDP IFN-β Poly(I:C) HMW Poly(I:C)-LyoVec LMW 0.1 RSV MDP RSV + MDP IFN-β HMW Poly(I:C)-LyoVec LMW A )
144 Chapter 8 A 20 * B 20 Ratio TNF-α Ratio IL-1β RSV RSV RSV MDP MDP RSV MDP MDP 0 RSV RSV RSV MDP MDP RSV MDP MDP A TNF-α IL-1β * Ratio 10 * * * * 5 * 0 H1N1 HRV-14 Reo-3 HAdV-3 142
145 et al. 22 in vitro
146 Chapter et al. et al. 144
147 in vivo
148 Chapter et al. et al. et al.
149 147 8 et al. et al. et al. et al. et al. et al.
150 Chapter 8 et al
151 Cytokines (pg/ml) IL-10 TNF-α IL-1β 0 RPMI RSV LTA LPS Flagellin CpG MDP RSV + LTA RSV + LPS RSV + Flagellin RSV + CpG RSV + MDP Cytokines (pg/ml) TNF-α IL-1β RPMI MDP HMW Poly(I:C)-LyoVec LMW Poly(I:C)-LyoVec HMW ssrna40-lyovec Poly(I:C) HMW + MDP Poly(I:C)-LyoVec LMW + MDP Poly(I:C)-LyoVec HMW + MDP ssrna40-lyovec + MDP Cytokines (pg/ml) RPMI MDP LPS LPS + MDP Cytokines (pg/ml) RPMI MDP R848 R848+ MDP A 8 149
152 Chapter 8 Cytokines (pg/ml) TNF-α IL-1β 0 RPMI + RPMI RPMI + RSV RPMI + MDP RSV + RPMI RSV + RSV RSV + MDP MDP + RPMI MDP + RSV MDP + MDP A 8 TNF-α (pg/ml) IL-1β (pg/ml) RPMI RPMI Monocytes Lymphocytes RSV RSV MDP MDP RSV+MDP RSV+MDP LPS Ratio * LPS TNF-α IL-1β 150
153 Cytokines (pg/ml) TNF-α IL-1β RPMI MDP H1N1 HRV-14 Reo-3 HAdV-3 MDP + H1N1 MDP + HRV-14 MDP + Reo-3 MDP + HAdV
154
155
156 Chapter 9 Streptococcus pneumoniae S. pneumoniae 9 154
157 S. pneumoniae and RSV disease severity Streptococcus pneumoniae S. pneumoniae S. pneumoniae S. pneumoniae in vitro 14 S. pneumoniae S. pneumoniae 15 S. pneumoniae S. pneumoniae 9 155
158 Chapter S. pneumoniae..
159 S. pneumoniae and RSV disease severity S. pneumoniae
160 Chapter 9 ). a a NS NS a NS a NS a S. pneumoniae S. pneumoniae 158
161 S. pneumoniae and RSV disease severity A 15 RSV load (Ct value) B present absent 10 5 MMP-9 (pg/ml) IL-6 (pg/ml) present absent 10 2 present absent C Patients (%) 100 Mild n=13 n=14 Moderate 80 Severe 60 n=34 n= n=8 present n=55 n=17 absent n=50 A S. pneumoniae S. pneumoniae ) 159
162 Chapter 9 A Sp (copies/ml) p = r = RSV load (Ct value) 15 B Sp (copies/ml) p = 0.02 r = MMP-9 (pg/ml) Sp (copies/ml) IL-6 (pg/ml) 9 C Sp (copies/ml) ** Mild Moderate Severe * A 0.01).
163 S. pneumoniae and RSV disease severity S. pneumoniae. H. ). S. pneumoniae S. pneumoniae S. pneumoniae. A Sp colonization (%) n=19 n=23 n=19 n=23 present absent B SP (copies/ml) C SP (copies/ml) 5x10 7 4x10 7 3x10 7 2x10 7 1x % unchanged 38% up 37% down 9 0 acute recovery 10 2 acute recovery 0 acute recovery A). ).
164 Chapter 9 S. pneumoniae S. pneumoniae. 9
165 S. pneumoniae and RSV disease severity S. pneumoniae S. pneumoniae S. pneumoniae S. pneumoniae M. catarrhalis H. S. aureus. S. pneumoniae S. pneumoniae S. pneumoniae. In 9
166 Chapter 9 9 vitro S. pneumoniae S. pneumoniae S. pneumoniae in vitro S. pneumoniae S. pneumoniae S. pneumoniae S. aureus M. catarrhalis
167 S. pneumoniae and RSV disease severity S. pneumoniae S. pneumoniae. S. pneumoniae S. pneumoniae 9
168 Chapter 9 9
169 S. pneumoniae and RSV disease severity 9
170 Chapter 9 9
171 S. pneumoniae and RSV disease severity S. pneumoniae a A SP colonization (%) n=7 n=8 n=16 n=15 n=25 n=9 n=15 n=21 n=11 n=15 n=11 n=16 <1m 1-2m 2-3m 3-6m 6-12m >12m present absent B HI colonization (%) <1m 1-2m 2-3m 3-6m 6-12m >12m present absent S. pneumoniae A H. n=7 n=8 n=8 n=23 n=14 n=20 n=11 n=25 n=4 n=22 n=8 n=19 9
172 Chapter 9 A RSV load (Ct value) present absent B MMP-9 (pg/ml) IL-6 (pg/ml) present absent 10 2 present absent 9 C Patients (%) 100 Mild n=20 n=7 Moderate 80 Severe 60 n=38 n= n=18 present n=76 n=7 absent n=29 A) H. 170
173 S. pneumoniae and RSV disease severity A SP load (copies/ml) <1m 1-2m 2-3m 3-6m 6-12m >12m B HI load (copies/ml) <1m 1-2m 2-3m 3-6m 6-12m >12m S. pneumoniae A A B C Hi (copies/ml) Hi (copies/ml) Hi (copies/ml) RSV load (Ct value) MMP9 (pg/ml) Mild Moderate Severe Hi (copies/ml) IL-6 (pg/ml) 9 A 171
174 Chapter 9 A 10 8 B 10 5 *** * MMP-9 (pg/ml) IL-6 (pg/ml) *** *** 10 5 Acute Recovery Control 10 2 Acute Recovery Control A 9 172
175
176
177
178 Chapter 10 10
179
180 Chapter Firmicutes Lactobacillus Bacillus Clostridium BacteroidetesBacteroides) ProteobacteriaEscherichia et al. 22 Streptococcus pneumoniae Staphylococcus aureus Clostridial 25 Bacteroides fragilis ). 178
181 Intestines Respiratory Tract Lumen Microbiota Virus Virus Microbiota Outer mucus layer Inner mucus layer Antimicrobial peptides MAMPs Antibodies Antibodies MAMPs Antimicrobial peptides Epithelial cells Lamina propia Local training of immune cells Local training of immune cells Vein Reduced/enhanced viral pathogenesis Reduced/enhanced viral pathogenesis Systemical training of immune cells. Firmicutes Staphylococcus Corynebacterium Propionibacterium Firmicutes Proteobacteria Bacteroidetes Streptococcus Neisseria Haemophilus Lachnospira Firmicutes Proteobacteria Bacteroidetes Streptococcus Staphylococcus Corynebacterium Neisseria Prevotella
182 Chapter Moraxella, Haemophilus, Streptococcus, Proteobacteria, et al. 29 Flavobacteria, Dolosigranulum, Firmicutes, Proteobacteria/Fusobacteria Corynebacterium, Neisseria Bacteroidetes, Bacteroidetes/Firmicutes Fusobacteria - Lactobaccillus, Prevotella, Sneathia et al. Staphylococcus, Corynebacterium, Propionibacterium - Moraxella, Streptococcus, Staphylococcus, Corynebacterium, Flavobacterium et al. 180
183 Propionibacterium, Staphylococcus, Corynebacterium, et al. - Firmicutes Firmicutes Staphylococcus, Propionibacterium, Corynebacterium - et al. Firmicutes, - Streptococcus, Staphylococcus, Neisseria et al. Corynebacterium, Propionibacterium, Streptococcus, Staphylococcus, Variovorax, Moraxella Firmicutes, Proteobacteria et al. Corynebacterium, Dolosigranulum, Staphyloccocus, Lactobacillus, Propionibacterium, Gardnerella, Anaerococcus, Prevotella Firmicutes, Proteobacteria, Bacteroidetes et al. - Staphylococcus, Propionibacterium, Corynebacterium, Streptococcus, Veillonella, Prevotella et al. - Prevotella, Streptococcus, Neisseria, Fusobacterium, Acidaminococcus et al. Bacteroidetes, Prevotella, Veillonella, Streptococcus - Firmicutes et al. Pseudomonas, Streptococcus, Prevotella, Fusobacterium et Proteobacteria, al. 40 Firmicutes, Bacteroidetes - Streptococcus, Prevotella, Veillonella et al
184 Chapter Pseudomonas Streptococcus Prevotella Fusobacterium Haemophilus Veillonella Porphyromonas Mycoplasma pulmonis 47. et al. 50 Viellonella Haemophilus Moraxella Prevotella Haemophilus 182
185 Enhanced Reduced Infection LPS coated virus Enhanced viral infection LPS stimulation Reduced viral infection Immune Response Viral infection MDP stimulation Enhanced cytokine response Reduced cytokine response Pneumococcus Viral infection et al et al
186 Chapter Lactobacillus plantarum 57 Lactobacillus et al. 184
187 ).. Staphylococcal S. pneumoniae In vitro. In vitro. Streptococcus viridans
188 Chapter 10 S. pneumoniae Lactobacilli Enterobacteria Bacteroides. Lactobacillus Prevotella Staphylococcus Corynebacterium)
189 Lactobacillus Bacteroides. Bacteroidetes 89. Bacteroidetes et al et al. 29 Proteobacteria Firmicutes Bacteroidetes Fusobacteria. Proteobacteria Fusobacteria Bacteroidetes Firmicutes et al
190 Chapter et al. et al. et al. Staphyloccous aureus Staphylococcal et al. 49 In vitro et al. 188
191 et al. 54 et al. 74 Lactobacillus casei L. casei et al. 58 et al. 59 Lactobacillus plantarum Lactobacillus plantarum et al. 57 Staphylococcus aureus et al. 75 Staphylococcus aureus et al. et al. et al. Lactobacillus rhamnosus L. rhamnosus et al. 11 Streptococcus viridans Streptococcus viridans et al. et al. 70 Streptococcus pneumoniae Streptococcus pneumoniae et al. S. pneumonia et al. Streptococcus pneumoniae Lactobacillus gasseri, et al
192 Chapter Bacteroides fragilis 95. Lactobacilli Lactobacillus casei
193
194 Chapter et al. et al. et al. et al. et al. et al. et al. et al. et al. 192
195 et al. et al. et al et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. 10
196 Chapter et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. 194
197 et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al
198 Chapter 10 et al. et al. 10
199
200
201
202 Chapter in vitro 200
203 Summary and general discussion IgA Antibodies IgG P art I Chemokines neutrophils RSV Epithelial cells IL-8 CCL-4 CXCL10 monocytes lymfocytes Cytokines Immune cells Microbiota macrophages TNFα IL-1β IL-6 MMP-9 IFNγ IL-10 DC s Part bacterial ligands II in vivo in vitro
204 Chapter In ). In In in vitro ). 202
205 Summary and general discussion In 24 ). Non-specific IgG RSV-specific non-neutralizing IgG RSV-specific neutralizing IgG neutrophils? CXCL10 RSV monocytes 11
206 Chapter In. 204
207 Summary and general discussion Gram negative LPS macrophages lymfocytes Gram positive RSV monocytes MDP IL-1β TNFα S. pneumoniae 11 MMP-9 S. pneumoniae 205
208 Chapter 11 S. pneumoniae S. pneumoniaes. pneumoniae S. pneumoniae in vivo in vitro M. catarrhalis S. aureus ). 11
209 Summary and general discussion P. gingivalis
210 Chapter
211 Summary and general discussion et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. et al et al
212 Chapter et al. et al. et al. et al. et al. et al. et al. et al. 5. et al
213 Summary and general discussion et al. et al. et al. et al. et al. et al
214
215
216 Chapter
217 12 215
218 Chapter Chemokines Cytokines CXCL10 neutrofielen lymfocyten monocyten IFNγ MMP-9 macrofagen DC s IL-8 CCL-4 IL-10 TNFα IL-1β IL-6 I eel D II Deel IgA IgG RSV Immuun cellen Epitheel cellen Antistoffen Microbioom bacteriele liganden
219 in vitro in vivo in vitro In ). In
220 Chapter in vitro ). 218
221 Niet-specifiek IgG RSV-specifiek niet-neutralizerend IgG RSV-specifiek neutralizerend IgG neutrofielen? CXCL10 RSV monocyten
222 Chapter In 220
223 S. pneumoniae S. pneumoniae S. pneumoniae Gram negatief LPS macrofagen lymfocyten Gram positief RSV monocyten MDP IL-1β TNFα S. pneumoniae MMP-9 S. pneumoniae
224 Chapter 12 S. pneumoniae M. catarrhaliss. aureus in vitro in vivo in vitro ). )
225 P. gingivalis 12
226 Chapter
227 12
228 Dankwoord
229 Dankwoord 227
230 Dankwoord 228
231 Dankwoord 229
232 /IAI # # * #
233
234
235 Curriculum Vitae
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237
ACTIVATION AND EFFECTOR FUNCTIONS OF CELL-MEDIATED IMMUNITY AND NK CELLS. Choompone Sakonwasun, MD (Hons), FRCPT
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