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Metabolic Reprogramming and Infectious Diseases

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Essential Aspects of Immunometabolism in Health and Disease

Abstract

Cellular organization is possible through metabolic processes that ensure the construction of biomass and energy supply. Central metabolic pathways use sensors to monitor nutrient availability and environmental changes. Metabolic sensors orchestrate environment-driven metabolic adaptations according to the cellular condition. Although the role of metabolism in the immune response has been established for many decades, only in recent years have researchers turned their interest to investigate metabolic changes in immune cells, setting the field of immunometabolism. Early in vitro studies were instrumental in uncovering mechanisms that induce a metabolic reprogramming required for an effective immune response, mainly in macrophages and dendritic cells. Also, in vitro studies have shown a metabolic shift during T cell activation and proliferation. However, such approaches may not reflect the metabolic complexity within an integrated organism with changes in partial oxygen pressure, pH, inflammation and nutrient gradient. Besides that, metabolic changes can affect both microenvironments and promote systemic inter-organ communication. Therefore, the immunometabolic study at specific sites is crucial to understand the outcome of infections, tumors, non-infectious inflammation and tissue repair. In this chapter, we will address the metabolic reprogramming in tissue-specific immune cells during host infection. At first, we will introduce the functioning of the immune system in barrier tissues that are the gateway to pathogens.

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Abbreviations

ACL:

ATP-dependent Citrate Lyase

AMPK:

AMP-activated protein kinase

AMPs:

Antimicrobial peptides

AMs:

Alveolar macrophages

Arg -1:

Arginase-1

ASN:

Asparagine

BCG:

Baccillus Calmette-Guérin

COVID-19:

Coronavirus disease 2019

DCs:

Dendritic cells

FAS:

Fatty Acid Synthesis

GALT:

Gut-Associated Lymphoid Tissue

GAS:

Group A Streptococcus

GLUT1:

Glucose Transporter 1

HIF:

αHypoxia-Inducible Factor 1-Alpha

HK2:

Hexokinase 2

IBPs:

Intracellular Bacterial Pathogens

IFNs:

Interferons

IgA:

Immunoglobulin A

IgG:

Immunoglobulin G

IL:

Interleukin

ILCs:

Innate lymphoid cells

ILFs:

Isolated Lymphoid Follicles

JE:

Junctional epithelium

LPS:

Lipopolysaccharide

MALT:

Mucosa-associated lymphoid tissue

MHC:

Major Histocompatibility Complex

MIF:

Migration Inhibitory Factor

MS:

Multiple Sclerosis

mTOR:

Mammalian Target of Rapamycin

mTORC1:

Mammalian Target of Rapamycin complex 1

MV:

Measles Virus

NETs:

Neutrophil Extracellular Traps

NK:

Natural killer

NLRP3:

NLR family pyrin domain containing 3

NO:

Nitric Oxide

Nrf2:

Nuclear Factor erythroid-derived 2

OAA:

Oxaloacetate

OXPHOS:

Oxidative Phosphorylation

PAMPs:

PathogenAssociated Molecular Patterns

PDK1 :

Phosphoinositide-Dependent Kinase 1

PFK1 :

Phosphofructokinase 1

PGE2:

Prostaglandin E2

PI3K :

Phosphoinositide-3 Kinase

pIgA:

Polymeric Immunoglobulin A

pIgR:

Polymeric immunoglobulin receptor

PIP3 :

Phosphatidylinositol-3,4,5-Trisphosphate

PKM2:

Pyruvate Kinase M2

PPARδ:

Peroxisome Proliferator-Activated Receptor Gamma

PPP:

Pentose Phosphate Pathway

PPs:

Peyer’s Patches

PRRs:

Pattern Recognition Receptors

ROS :

Reactive Oxygen Species

SARS-CoV-2:

Respiratory Syndrome Coronavirus 2

SH2:

Src Homology 2

TAC:

Tricarboxylic Acid Cycle

TGF-β:

Transforming growth factor-β

Th:

T helper

TLRs:

Toll-like receptors

Tr1:

Type 1 Regulatory T cells

Tregs:

Regulatory T cells

TRMs :

Tissue-Resident Macrophages

UTIs:

Urinary tract infections

α-KG:

α-Ketoglutarate

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Authors and Affiliations

  1. Laboratory of Immunology of Infectious Diseases, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil

    Érika Machado de Salles

  2. Laboratory of Mucosal Immunology, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil

    Bárbara Cristina Pizzolante & Denise Morais da Fonseca

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  1. Érika Machado de Salles
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  2. Bárbara Cristina Pizzolante
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  3. Denise Morais da Fonseca
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Correspondence to Denise Morais da Fonseca .

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Editors and Affiliations

  1. Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil

    Niels Olsen Saraiva Camara

  2. Department of Pharmacology, University of São Paulo, São Paulo, Brazil

    Jose C Alves-Filho

  3. Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil

    Pedro Manoel Mendes de Moraes-Vieira

  4. Bernardo’s Lab, Center for Natural and Human Sciences, Federal University of ABC, São Paulo, Brazil

    Vinicius Andrade-Oliveira

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de Salles, É.M., Pizzolante, B.C., da Fonseca, D.M. (2022). Metabolic Reprogramming and Infectious Diseases. In: Camara, N.O.S., Alves-Filho, J.C., Moraes-Vieira, P.M.M.d., Andrade-Oliveira, V. (eds) Essential Aspects of Immunometabolism in Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-030-86684-6_8

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