Essential Aspects of Immunometabolism in Health and Disease

Preface
Contents
Contributors
Overview of Immune Responses
	1 General Aspects of the Immune System
	2 Cells of the Immune System
	3 Innate Immunity
	4 Adaptive Immunity
		4.1 Cell-Mediated Adaptive Immune Responses
		4.2 Humoral Adaptive Immune Responses
	5 Final Remarks
	References
Metabolic Pathways and Cell Signaling
	1 Overview of Metabolic Pathways
	2 The Mechanistic Logic of Metabolic Signaling
	3 Nutrient-Sensing Signaling Pathways
		3.1 Lipid Sensing
		3.2 Amino Acid Sensing
		3.3 Carbohydrate Sensing
	4 Extracellular Signals that Regulate Fuel Metabolism
	5 Pathway Crosstalk in the Regulation of Metabolism
	References
Mitochondrial Biogenesis and Dynamics in Health and Disease
	1 Introduction
	2 Mitochondrial Biogenesis
		2.1 Transcription Factors Regulating Mitochondrial Biogenesis
		2.2 The Role of Transcriptional Coactivators in Mitochondrial Biogenesis: PGC-1 Family
	3 Mitochondrial Dynamics
		3.1 Mitochondrial Fusion
		3.2 Mitochondrial Fission
	4 Mitochondrial Dynamics in Health and Disease
	5 Concluding Remarks
	References
Metabolic Pathways in Immune Cells Commitment and Fate
	1 Introduction
	2 Metabolic Pathway Impact on T Cell Differentiation and Function
	3 Effector Versus Memory Cells
	4 B Cell Metabolism
	5 Macrophages M1/M2
	6 Dendritic Cells
	7 Concluding Remarks
	References
Metabolic Profile of Innate Immune Cells
	1 Macrophages and Monocytes
		1.1 M1 and M2 Subset Macrophages
		1.2 Immunometabolism in Macrophages Effector Functions
	2 Monocytes
	3 Dendritic Cell Subsets
		3.1 Bone-Marrow Dendritic Cells (BMDC) and Monocyte-Derived Dendritic Cells (MoDC)
		3.2 Plasmacytoid Dendritic Cells (pDC)
		3.3 Tolerogenic DC
	4 Neutrophils
	5 Other Granulocytes
	6 Innate Lymphoid Cells
		6.1 Group 1—Innate Lymphoid Cells (ILC)-Intrinsic Metabolism
		6.2 Group 2—ILC-Intrinsic Metabolism
		6.3 Group 3 ILC-Intrinsic Metabolism
	References
Metabolic Profile of Adaptive Immune Cells
	1 Introduction
	2 Cellular Metabolism in T Cells
		2.1 T Cell Metabolism During Ontogeny and Activation
		2.2 T Cell Metabolism During Functional Differentiation
		2.3 T Cell Metabolism During Migration
		2.4 T Cell Metabolism in the Contraction Phase
		2.5 T Cell Metabolism During Exhaustion
	3 Cellular Metabolism in B Cells
		3.1 B Cell Metabolism During Ontogeny
		3.2 B Cell Metabolism During Activation in GCs
		3.3 Plasma Cells Differentiation and Antibody Production
	4 Concluding Remarks
	References
Obesity, Metabolic Syndrome and Inflammation
	1 Introduction
	2 Adipose Tissue Inflammation and Obesity
	3 The Role of Tumor Necrosis Factor (TNF) in Obesity and Insulin Resistance
	4 The Role of Retinol-Binding Protein-4 (RBP-4) in Insulin Resistance
	5 The Role of Leptin in Obesity and Insulin Resistance
	6 Immune Cell Function Within Adipose Tissue
	7 The Role of the Gut in Obesity and Inflammation
	8 The Gut is an Immunoendocrine Organ
		8.1 Proglucagon-Derived Peptides: Glucagon-Like Peptides-1 and -2 (GLP-1 and GLP-2)
		8.2 Glucagon-Like Peptide-2
	9 The Gut Microbiome and Its Role in Obesity
	10 The Role of Intestinal Immune Cells in Obesity and Insulin Resistance
	11 Conclusions
	References
Metabolic Reprogramming and Infectious Diseases
	1 Barrier Tissues as Major Sites for Pathogen Entrance
		1.1 Skin Barrier
		1.2 Airway Barrier
		1.3 Urinary Tract Barrier
		1.4 Oral and Intestinal Barriers
	2 Consequences of Infection for the Tissue Immune Homeostasis
	3 Effects of Infection in the Immune Cell Metabolism
	4 Metabolic Reprogramming of T Cells to Protect Against Infections
	5 Modulation of Immune Cell Metabolism by Pathogens
	6 Therapy Targeting Cell Metabolism to Control Infections
	References
Metabolic Reprogramming and Cancer
	1 A Brief Historical Perspective
	2 Cancer Cells
		2.1 Oncogenes and Tumor Suppressor Genes
		2.2 Cell Cycle Control
		2.3 Cancer Cell Metabolism
	3 Microenvironment and Signaling Pathways Regulating Cancer Cell Metabolism
		3.1 HIF-1
		3.2 c-MYC
		3.3 PI3K/AKT/mTOR
		3.4 Tp53
	4 Effects of Tumor Cell Metabolism on Cancer Progression
	5 Final Remarks
	References
Adipose Tissue and Immuno-Metabolic Regulation
	1 Introduction
	2 Lipogenesis
	3 White Adipose Tissue (WAT)
	4 Brown Adipose Tissue (BAT)
	5 White Adipose Tissue and Obesity
	6 Adipocytes as Endocrine Cells
	7 Leptin
	8 Adiponectin
	9 Retinol-Binding Protein 4 (RBP4)
		9.1 Adipose Tissue Immune Cells
		9.2 Macrophages
		9.3 Adipose Tissue Macrophages
		9.4 Other Innate Immune Cells
		9.5 B Cells
		9.6 T Cells
		9.7 Adipose Tissue Inflammation
		9.8 Inflammation and Type 2 Diabetes
		9.9 Inflammation and Heart Disease
		9.10 Human Trials in Anti-Inflammatories
	References
Immune Regulation of Adipose Tissue Browning
	1 Introduction
	2 Immune Cells in Adipose Tissue
		2.1 Myeloid Cells
		2.2 Lymphoid Cells
	3 Immune Cell Mediators and Their Role in Browning
	4 Novel Mechanisms of Intercellular Communication in Adipose Tissue
	5 Conclusions
	References
Physical Exercise and Metabolic Reprogramming
	1 Metabolic Reprograming with Aerobic and Resistance Exercise
	2 Exercise and Immune System
	3 Exercise for the Treatment and Prevention of Metabolic Disease
	4 Exercise for the Prevention and Treatment of Cancer
	5 Conclusion
	References
Immunometabolism and Organ Transplantation
	1 Introduction
	2 Metabolic Pathways in the Context of the Immune Response in Transplantation
	3 Immunometabolic Events in Transplantation
		3.1 Metabolic Changes in Ischemia/Reperfusion
		3.2 Metabolic Regulation During Acute Rejection
		3.3 Metabolic Features in Chronic Rejection and Fibrosis
		3.4 Role of Immune Cell Metabolism in Tolerance Induction
	4 Key Metabolic Sensors in Transplantation
	5 Sirtuins as “Metabolic Sensors and Regulators” in Transplantation
	6 Trained Immunity in Organ Transplantation
	7 Metabolic Conditioning of Microbiome in Transplantation
	8 Final Conclusions
	References