Toll-like Receptors: Roles in Infection and Neuropathology

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