Toll-like Receptors: Roles in Infection and Neuropathology (eBook)

Title page 4
Copyright Page 5
Contents 7
Contributors 8
Overview of Toll-Like Receptors in the CNS 11
1 Historical Background of TLRs 12
2 TLR Subtypes and Ligand Classification 14
2.1 Extracellular TLRs and CNS Expression Patterns 14
2.2 Intracellular TLRs and CNS Expression Patterns 16
3 TLR Signaling Pathways 17
4 Highlights of Contributing Chapters and Emerging Concepts 18
References 20
Toll-Like Receptors in Bacterial Meningitis 25
1 Introduction 26
2 An Immunological Approach to the Cerebrospinal Fluid Compartment 27
3 Bacteriologic Profile of Community-Acquired Bacterial Meningitis 30
4 Host Cellular Sensors of Meningeal Pathogens 31
4.1 Immune Recognition of S. pneumoniae In Vitro 35
4.2 Immune Recognition of N. meningitidis In Vitro 37
4.3 Immune Recognition of S. agalactiae In Vitro 38
4.4 Immune Recognition of L. monocytogenes In Vitro 39
5 Role of TLRs in Pneumococcal Meningitis 39
6 Conclusions 43
References 44
Toll-Like Receptors in Brain Abscess 51
1 Etiopathogenesis of Brain Abscess 53
2 Experimental Brain Abscess Model 54
3 Importance of TLRs in Glial Recognition of S. aureus 55
3.1 TLR and Microglial Responses to S. aureus 56
3.2 Astrocytes and TLR2-dependent Recognition of S. aureus 58
3.3 Cytokine Regulation of TLR2 Expression in Glia 58
3.4 Potential Contributions of Other TLRs to S. aureus Recognition by Glia 59
4 Impact of TLR Signaling on Immune Responses During Brain Abscess Development 60
4.1 Influence of TLRs on Innate Immunity in Brain Abscesses 60
4.2 Relationship Between TLR2 and Adaptive Immunity in Brain Abscesses 63
4.3 Concept of a “Pathogen–Necrosis–Autoantigen Triad” 64
5 Summary 66
References 66
Toll-Like Receptors in CNS Viral Infections 72
1 Toll-Like Receptors (TLRs) That Are Viral Sensors 74
2 Toll-Like Receptor 3 (TLR3) 75
2.1 TLR3 Signaling 76
2.2 TLR3 Versus Cytosolic dsRNA Sensors 78
2.3 TLR3 and CNS Glial Cells 78
2.4 Mechanisms of Antiviral Immunity Elicited by TLR3 In Vitro 80
2.5 Antiviral Immunity Elicited by TLR3 In Vivo 82
2.6 TLR, Adaptive Immunity and Autoimmune Responses 83
2.7 Effect of Systemic or Intracerebral Poly I:C on Brain Function and Inflammation 84
3 Roles for Other TLRs in Virus Infections in the CNS 85
4 Conclusions and Future Directions 86
References 87
Toll-Like Receptors in CNS Parasitic Infections 91
1 CNS Parasitic Infections and Burden on Society 92
2 Immunopathogenesis of Parasitic Infections 93
3 TLRs in CNS Parasite Infection 95
3.1 Role of TLRs in CNS Protozoa Infections 96
3.1.1 Cerebral Malaria 96
3.1.2 Toxoplasmosis 98
3.1.3 Sleeping Sickness 100
3.2 Role of TLRs in CNS Helminth Infections 101
3.2.1 Neurocysticercosis (NCC) 101
3.2.2 River Blindness/Onchocerciasis 105
4 Conclusions and Perspectives 106
References 107
Toll-Like Receptors in Neurodegeneration 113
1 Background 114
2 Pathogen Recognition Versus Homeostasis 115
3 Inflammation and Degeneration: Immune Concepts 115
4 Beneficial Outcomes of TLR Signaling in Microglia 117
4.1 Wallerian Degeneration 117
4.2 Nerve Injury 117
5 TLR-Driven Neurotoxicity 118
5.1 Neuronal Injury 118
5.2 Ischemia 119
5.3 Neurodegenerative Disorders 119
5.4 Infection 120
5.5 TLR-Driven Gliotoxicity 120
6 Strength of Signal: A Hypothesis 121
7 Clinical Correlates 122
8 TLR2/4 Expression by Astrocytes 123
8.1 Astrocytes in Neurodegeneration 123
9 Other TLRs 124
10 Conclusions 125
References 125
Toll-Like Receptors in Spinal Cord Injury 129
1 Pathology and the Inflammatory Response Triggered by Traumatic SCI 130
2 TLRs Promote CNS Degeneration and Regeneration 131
2.1 Toll-Like Receptors and DAMPs 131
2.2 Divergent Functions are Triggered by Select TLRs 133
3 The Effects of Activating TLRs In Vivo in Spinal Cord 135
4 TLR Activation and SCI 136
5 Conclusions 138
References 139
Toll-Like Receptors in Alzheimer’s Disease 145
1 Alzheimer’s Disease 146
2 Inflammation and Alzheimer’s Disease 147
3 Innate Immunity in Alzheimer’s Disease 149
3.1 Increased TLR Expression 150
3.2 TLRs in Microglial Activation 151
3.3 TLRs in the Death of Neurons 154
3.4 TLRs and the Clearance of Ab from the Brain 155
4 Conclusions 156
References 157
Toll-Like Receptors in Multiple Sclerosis 162
1 Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis 163
2 Role of Pathogens in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis 165
3 Toll-Like Receptors: Role in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis 166
3.1 TLRs in MS and EAE: An Overview 166
3.2 TLRs in MS and EAE: The Current Understanding 168
4 Summary 171
References 171
Toll-Like Receptors in Peripheral Nerve Injury and Neuropathic Pain* 176
1 Introduction 177
2 TLRs in Peripheral Nerve Injury 178
2.1 Wallerian Degeneration After Nerve Injury 178
2.2 TLR Expression in the Peripheral Nervous System 180
2.3 TLRs in Traumatic Peripheral Nerve Injury 181
2.4 TLRs in Infectious Peripheral Neuropathy 182
3 TLRs in Neuropathic Pain 183
3.1 What is Neuropathic Pain? 183
3.2 Spinal Cord Glia as Key Players in Neuropathic Pain 184
3.3 Involvement of TLRs in Neuropathic Pain 185
3.4 Endogenous TLR Ligands Involved in Nerve Injury and Neuropathic Pain 187
4 Summary 188
References 188
Index 194