Current Topics in Innate Immunity II (Advances in Experimental Medicine and Biology, 946)

Annotation Mounting evidence in the past decade indicates that innate immunity mediates functions above and beyond first-line defense against infection. It is now appreciated that innate immune mechanisms are critically involved in the development of adaptive immunity and, moreover, the regulation of diverse physiological and homeostatic processes. The latter explains why deregulation of innate immunity may lead to pathological disorders that are not necessarily or directly related to host defense. This Volume compiles the latest advances in this rapidly evolving field as presented by eminent scientists at the 7th International Aegean Conference on Innate Immunity in Rhodes, Greece. It includes topics related to the biology and function of Toll-like and other pattern-recognition receptors, complement and its crosstalk with other physiological systems, inflammatory mechanisms and diseases, natural killer cells, and the cooperative interplay between innate and adaptive immune cells. This book is an excellent source of information for researchers and clinicians with interests in immunology, host-microbe interactions, and infectious and inflammatory diseases Preface Contents List of Contributors Pentraxins in Humoral Innate Immunity 1 Introduction 2 The Pentraxin Superfamily 3 The Short Pentraxins in Innate Immunity 4 The Long Pentraxin PTX3 4.1 Gene Organization and Expression 4.2 Protein Structure 4.3 Interaction with Complement and Fcγ Receptors 4.4 PTX3 in Pathogen Recognition and Inflammation 4.5 Self versus Modified Self-Discrimination 4.6 PTX3 Role in Tissue Remodelling 4.7 Diagnostic and Prognostic Potential of PTX3 in Infectious Disorders 5 Concluding Remarks References Galectins as Pattern Recognition Receptors: Structure, Function, and Evolution 1 Introduction 2 Structure and Biochemical Properties of Galectins 3 Biological Roles of Galectins in Development and Regulation of Immune Homeostasis 4 Galectins as Pattern Recognition Receptors 5 Some Microbial Pathogens and Parasites Subvert the Role of Galectins as PRRs 6 Conclusions References The Role of Innate Immunity in Trafficking of Hematopoietic Stem Cells—An Emerging Link Between Activation of Complement Cascade and Chemotactic Gradients of Bioactive Sphingolipids 1 Introduction 2 Stem Cell Mobilization 2.1 Stem Cell Mobilization as Part of Stress Response 2.2 Activation of Complement Cascade (CC) 2.3 Involvement of Granulocytes in Mobilization 2.4 Role of Sphingosine 1-Phosphate (S1P) 3 Stem Cell Homing 3.1 Conditioning for Transplantation Induces Proteolytic Microenvironment in BM 3.2 Conditioning for Transplantation Activates Complement Cascade (CC) in BM 4 Implications of “Priming Phenomenon” that Enhances Responsiveness of CXCR4 Receptor to SDF-1 Gradient 5 Conclusions References Interaction of the Microbiome with the Innate Immune Response in Chronic Wounds 1 Introduction 2 The Burden of Chronic Wounds 3 Surveying the Microbial Diversity of Chronic Wounds 4 The Skin is the First Line of Defense 5 The Innate Immune Response During Normal Wound Healing 6 An Aberrant Innate Immune Response in Chronic Wounds 7 Conclusions and Perspectives References Pathogenic Microbes and Community Service Through Manipulation of Innate Immunity 1 Introduction 2 Keystone Pathogens in the Periodontal Biofilm 3 Porphyromonas gingivalis: Interfering with Host Immunity for the Microbial “Common Good”? 3.1 The LPS as a Tool to Antagonize TLR4 3.2 The Gingipains as a Means to Manipulate Complement and Leukocytes 3.3 Fimbriae: Multitasking Beyond Colonization 4 Is the Presence of P. gingivalis Benefiting Other Periodontal Bacteria? 5 Perspectives and Conclusions References A Conserved Host and Pathogen Recognition Site on Immunoglobulins: Structural and Functional Aspects 1 Immunoglobulins 2 A Conserved Binding Site at the Junction of Two Constant Domains 3 Functional Consequences of Host Proteins Binding to the Conserved Site on Immunoglobulins 3.1 The Neonatal Fc Receptor (FcRn) is Involved in Transplacental Transport of Maternal IgG and Maintaining Plasma IgG Levels 3.2 Tripartite Motif-Containing 21 (TRIM21) PRYSPRY Domain Binds IgG-Fc 3.3 Autoantibodies Against IgG often Target the CH2–CH3 Domain Junction 3.4 Myeloid Fc Receptor for IgA Recognizes the CH2–CH3 Domain Junction 3.5 The CH3–CH4 Domain Junction of IgM is Analogous to the CH2–CH3 Site on IgG and IgA 4 Hijacking of Immunoglobulins by Pathogens: Recognition of the Conserved Target Site 4.1 Bacterial Proteins A and G Target the CH2–CH3 Junction of IgG 4.2 An Fc Receptor for IgG from HSV-1 is Implicated in Antibody Bipolar Bridging 4.3 Bacterial IgA-Binding Proteins Interact with the Common CH2–CH3 Binding Site and may be Implicated in Evasion of IgA Immunity 4.4 A Malarial Surface Antigen can Bind Polymeric IgM by Residues in the CH4 Domain 4.5 Convergent Recognition of the CH2–CH3 Domain Junction 5 Pathogen Proteins as Bridges between the Adaptive and the Innate Immune Systems 6 Concluding Remarks References Advances in Understanding the Structure, Function, and Mechanism of the SCIN and Efb Families of Staphylococcal Immune Evasion Proteins 1 Complement-directed Immune Evasion by Staphylococcus aureus 2 Recent Developments Regarding the Staphylococcal Complement Inhibitor Family 2.1 Background 2.2 Structure and Active Sites of SCIN-A 2.3 Structure/Function Analysis of SCIN-A Binding to C3c/C3b 2.4 Structural/Functional Basis for SCIN-A Inhibition of C3 Convertase Activity 2.5 Structural Basis and Functional Consequences of SCIN-induced Dimerization of C3b 3 Recent Developments Regarding the Extracellular Fibrinogen-Binding Protein Family 3.1 Background 3.2 Structure/Function Analysis of Efb-C Binding to C3, C3b, and C3d 3.3 Allosteric Inhibition of C3 Convertase Function by Efb-C 3.4 Structure/Function Studies of the Efb Homologous Protein, Ehp/Ecb 3.5 Disruption of Adaptive Immune Engagement by Efb and Ehp 4 Conclusions and Future Directions References Granzyme B: A New Crossroad of Complement and Apoptosis 1 Introduction: Interactions of the Complement System and Apoptosis 2 Material and Methods 2.1 Reagents 2.2 In Vitro Cleavage of C3 and C5 2.3 Detection of C3a and C5a by Western Blot 2.4 ELISA Analysis of C3a and C5a 2.5 Neutrophil (PMN) Isolation and Chemotaxis Assay 2.6 Antibodies for the Flow Cytometry Analysis 2.7 Intracellular Staining for Granzyme B and Flow Cytometry Analysis 2.8 Statistics 3 Results 3.1 Cleavage of C3 by Granzyme B 3.2 Cleavage of C5 by Granzyme B 3.3 Granzyme B in Leukocytes of Trauma Patients 4 Discussion References Role of C3, C5 and Anaphylatoxin Receptors in Acute Lung Injury and in Sepsis 1 Acute Lung Vascular Injury Following Systemic Activation of Complement 2 Complement in Experimental and Clinical Acute Lung Injury 3 Lessons Learned in C3−/− Mice 4 Role of C5aR and C5L2 in IgGIC ALI 5 Evidence for Regulatory Roles of C5, C3a, C5a, C3aR and C5aR in Inflammation 6 Roles of C3, C5 and C5a Receptors in Polymicrobial Sepsis 7 Possible Translational Applications to Human Sepsis References Complement Involvement in Neovascular Ocular Diseases 1 Eyeing the Complement System 1.1 The Complement System 1.2 Classical Complement Pathway 1.3 Alternative Complement Pathway 1.4 Lectin Complement Pathway 1.5 Late Steps of Complement Activation 1.6 Membrane-Bound Mediators of Complement or Complement Inhibitors 2 Age-Related Macular Degeneration 2.1 The Complement System in AMD 2.2 Anti-Complement Drugs in AMD 3 Retinopathy of Prematurity 3.1 Inflammation in ROP 3.2 The Complement System in ROP 4 Diabetic Retinopathy 4.1 Inflammation in DR 4.2 Involvement of the Complement System in Diabetic Retinopathy 5 Conclusions References Platelets, Complement, and Contact Activation: Partners in Inflammation and Thrombosis 1 Background 1.1 The Complement System 1.2 The Contact System 1.3 Platelets 1.4 Proteoglycans 1.5 Chondroitin Sulfate (CS) 1.6 Platelet–Leukocyte Interactions 2 Platelet–Complement Interactions 2.1 Activation of Platelets by Complement Activation Products 2.2 Binding of Complement Components to Activated Platelets 2.3 Complement Activation Triggered by CS-A Released from Activated Platelets 2.4 Interaction Between C1q, Complement Regulators, and CS-A 2.5 Model for the Interaction Between Platelets and Complement 3 Interactions of Cells and Cellular Components with the Contact Activation System 3.1 Cell-Induced Contact Activation 3.2 Platelet-Induced Contact Activation 4 Conclusions References Nuclear Factor-κB in Immunity and Inflammation: The Treg and Th17 Connection 1 The Rel/Nuclear Factor-κB (Rel/NF-κB) Family of Transcription Factors and Immune Regulation 2 NF-κB and Treg Cell Development 2.1 Treg Development is Markedly Diminished in c-Rel-Deficient Mice (Ruan et al. 2009) 2.2 c-Rel Orchestrates the Formation of a Foxp3-Specific Enhanceosome that Contains c-Rel, p65, NFAT, Smad, and CREB (Ruan et al. 2009) 3 NF-κB and Th17 Cell Response 3.1 T Cells Deficient in c-Rel or p65 are Significantly Compromised in Th17 Differentiation and Th17 Responses 3.2 The Rel−RORγΤ Axis that Drives Th17 Differentiation 3.3 c-Rel-Deficient Mice have Diminished Autoimmune Th17 Responses 4 Future Perspective References Function of Act1 in IL-17 Family Signaling and Autoimmunity 1 Introduction 2 IL-17 Family 3 Discovery of Act1 4 STIR Domain Superfamily 5 Act1 is a U-box Type E3 Ubiquitin Ligase 6 Epithelial Requirement of Act1 in IL-17 and IL-25 Mediated Lung Inflammation 7 Act1 in CNS Resident Cells 8 Act1, The Double-Edged Sword References Differential Effect of Inhibiting MD-2 and CD14 on LPS- Versus Whole E. coli Bacteria-Induced Cytokine Responses in Human Blood 1 Introduction 2 Materials and Methods 2.1 Bacterial Preparation 2.2 Inhibitors 2.3 Whole Blood Model of Sepsis 2.4 Cytokine and TCC Measurements 2.5 Transient Transfection and NF-κB Luciferase Assay 2.6 Statistics 3 Results 3.1 Effect of MD-2- and CD14-Inhibition on E. coli UpLPS-Induced Cytokine Response in Whole Blood 3.2 Effect of MD-2-, CD14- and Complement-Inhibition on Whole E. coli Bacteria-Induced Cytokine Response in Whole Blood 3.3 Effect of MD-2-, CD14- and Complement-Inhibition on Whole E. coli-Induced Chemokine Response in Whole Blood 3.4 Effect of MD-2-, CD14- and Complement-Inhibition on Whole E. coli-Induced IL-17 and IL-1ra Response in Whole Blood 3.5 Effect of MD-2-, CD14- and Complement-Inhibition on E. coli UpLPS and Whole Bacteria Induced Complement Activation in Whole Blood 3.6 Effect of Whole E. coli Bacteria and TLR Ligands on NFκB Activity 4 Discussion References Zebrafish: Model for the Study of Inflammation and the Innate Immune Response to Infectious Diseases 1 Introduction 2 Main Cells Involved in the Innate Immune Response in Zebrafish 3 Immune Genes Characterized in Zebrafish 4 Functional Ontogeny of the Immune System 5 Zebrafish as a Model for Infectious Diseases 6 Application of Genomics, Transgenesis and Other Tools in the Study of Infectious Diseases 6.1 Mutagenesis 6.2 Microarrays and Next-Generation Sequencing Methods 6.3 Transgenesis and RNAi 6.4 Chemical Genetic Screens 6.5 Imaging 6.6 Gnotobiotic Zebrafish 7 Some Examples of Application to Inflammatory Human Diseases 8 Conclusions References Monocyte-derived Inflammatory Dendritic Cells in the Granuloma During Mycobacterial Infection 1 Introduction 2 Development and Phenotype 3 Function of Monocyte-derived Inflammatory DCs During Infection 3.1 Mycobacteria 3.2 Other Bacteria 3.3 Viruses 3.4 Fungi 3.5 Protozoan 4 Conclusions References NK/DC Cross-talk in Anti-viral Response 1 Introduction 2 NK Cell Receptors 3 NK Cell Subsets in Peripheral Tissues and Lymphoid Organ 4 Cross-talk Between NK Cells and Dendritic Cells 5 NK/DC Cross-talk in CMV Infection 6 NK/DC Cross-talk in Influenza Infection References Innate-Adaptive Crosstalk: How Dendritic Cells Shape Immune Responses in the CNS 1 Introduction to Dendritic Cells and Their Subsets 2 Dendritic Cell Subsets Accumulate in the CNS During Neuroinflammation 2.1 Dendritic Cells in the Healthy CNS 2.2 Dendritic Cell Subset Accumulation in the CNS During Neuroinflammation 3 Mechanisms of Dendritic Cell Migration into the CNS 3.1 Regulation of DC Migration across the BBB: Adhesion Molecules 3.2 Regulation of DC Migration across the BBB: Chemokines and Growth Factors 3.3 Regulation of DC Migration across the Blood-CSF Barrier 4 Dendritic Cell Functions in the CNS 4.1 Dendritic Cells can be Positive or Negative Regulators of CNS Immunity 4.2 Dendritic Cells Migrate Out of the CNS to Deep Cervical Lymph Nodes 4.3 Dendritic Cells might Locally Restimulate Effector T-cells 4.4 Dendritic Cells Subsets Skew Effector T-cell Responses 5 Summary References Nutritional Immunity: Homology Modeling of Nramp Metal Import 1 In Defense of Host Metalome 2 Metabolism of Metals Scavenged from Ingested Corpses 3 Divalent Metal Import by Natural Resistance-associated Macrophage Proteins (Nramp) 4 A Phylogenetic Approach to Study Nramp Mechanism of Membrane Transport 5 Structural Origins of the Nramp Family 6 Structural Homology Among the LeuT Superfamily Connects the Nramp Family 7 Functional Implications for Nramp Immunological Roles References Index Pentraxins In Humoral Innate Immunity -- Galectins As Pattern Recognition Receptors: Structure, Function, And Evolution -- Role Of Innate Immunity In Trafficking Of Hematopoietic Stem Cells: An Emerging Link Between Activation Of Complement Cascade And Chemotactic Gradients Of Bioactive Sphingolipids -- Interaction Of The Microbone With The Innate Immune Response In Chronic Wounds -- Pathogenic Microbes And Community Service Through Manipulation Of Innate Immunity -- Conserved Host And Pathogen Recognition Site On Immunoglobulins: Structural And Functional Aspects -- Advances In Understanding The Structure, Function, And Mechanism Of The Scin And Efb Families Of Staphlyococcal Immune Evasion Proteins -- Granzmye B: A New Crossroad Of Complement And Appoptosis -- Role Of C3, C5 And Anaphylatoxin Receptors In Acute Lung Injury And In Sepsis -- Complement Involvement In Neovascular Ocular Diseases -- Platelets, Complement, And Contact Activation: Partners In Inflammation And Thrombosis -- Nuclear Factor-[delta]b In Immunity And Inflammation: The Treg And Th17 Connection -- Function Of Act1 In Il-17 Family Signaling And Autoimmunity -- Differential Effect Of Inhibiting Md-2 And Cd14 On Lps- Versus Whole E. Coli Bacteria-induced Cytokine Responses In Human Blood -- Zebrafish: Model For The Study Of Inflammation And The Innate Immune Response To Infectious Diseases -- Monocyte-derived Inflammatory Dendritic Cells In The Granuloma During Mycobacterial Infection -- Nk/dc Crosstalk In Anti-viral Response -- Innate-adaptive Crosstalk: How Dendritic Cells Shape Immune Responses In The Cns -- Nutritional Immunity: Homology Modeling Of Nramp Metal Import. Edited By John D. Lambris, George Hajishengallis. Includes Bibliographical References And Index.