Cargando…

Polarization of Macrophages in Insects: Opening Gates for Immuno-Metabolic Research

Insulin resistance and cachexia represent severe metabolic syndromes accompanying a variety of human pathological states, from life-threatening cancer and sepsis to chronic inflammatory states, such as obesity and autoimmune disorders. Although the origin of these metabolic syndromes has not been fu...

Descripción completa

Detalles Bibliográficos
Autores principales: Bajgar, Adam, Krejčová, Gabriela, Doležal, Tomáš
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917182/
https://www.ncbi.nlm.nih.gov/pubmed/33659253
http://dx.doi.org/10.3389/fcell.2021.629238
_version_ 1783657642277732352
author Bajgar, Adam
Krejčová, Gabriela
Doležal, Tomáš
author_facet Bajgar, Adam
Krejčová, Gabriela
Doležal, Tomáš
author_sort Bajgar, Adam
collection PubMed
description Insulin resistance and cachexia represent severe metabolic syndromes accompanying a variety of human pathological states, from life-threatening cancer and sepsis to chronic inflammatory states, such as obesity and autoimmune disorders. Although the origin of these metabolic syndromes has not been fully comprehended yet, a growing body of evidence indicates their possible interconnection with the acute and chronic activation of an innate immune response. Current progress in insect immuno-metabolic research reveals that the induction of insulin resistance might represent an adaptive mechanism during the acute phase of bacterial infection. In Drosophila, insulin resistance is induced by signaling factors released by bactericidal macrophages as a reflection of their metabolic polarization toward aerobic glycolysis. Such metabolic adaptation enables them to combat the invading pathogens efficiently but also makes them highly nutritionally demanding. Therefore, systemic metabolism has to be adjusted upon macrophage activation to provide them with nutrients and thus support the immune function. That anticipates the involvement of macrophage-derived systemic factors mediating the inter-organ signaling between macrophages and central energy-storing organs. Although it is crucial to coordinate the macrophage cellular metabolism with systemic metabolic changes during the acute phase of bacterial infection, the action of macrophage-derived factors may become maladaptive if chronic or in case of infection by an intracellular pathogen. We hypothesize that insulin resistance evoked by macrophage-derived signaling factors represents an adaptive mechanism for the mobilization of sources and their preferential delivery toward the activated immune system. We consider here the validity of the presented model for mammals and human medicine. The adoption of aerobic glycolysis by bactericidal macrophages as well as the induction of insulin resistance by macrophage-derived factors are conserved between insects and mammals. Chronic insulin resistance is at the base of many human metabolically conditioned diseases such as non-alcoholic steatohepatitis, atherosclerosis, diabetes, and cachexia. Therefore, revealing the original biological relevance of cytokine-induced insulin resistance may help to develop a suitable strategy for treating these frequent diseases.
format Online
Article
Text
id pubmed-7917182
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-79171822021-03-02 Polarization of Macrophages in Insects: Opening Gates for Immuno-Metabolic Research Bajgar, Adam Krejčová, Gabriela Doležal, Tomáš Front Cell Dev Biol Cell and Developmental Biology Insulin resistance and cachexia represent severe metabolic syndromes accompanying a variety of human pathological states, from life-threatening cancer and sepsis to chronic inflammatory states, such as obesity and autoimmune disorders. Although the origin of these metabolic syndromes has not been fully comprehended yet, a growing body of evidence indicates their possible interconnection with the acute and chronic activation of an innate immune response. Current progress in insect immuno-metabolic research reveals that the induction of insulin resistance might represent an adaptive mechanism during the acute phase of bacterial infection. In Drosophila, insulin resistance is induced by signaling factors released by bactericidal macrophages as a reflection of their metabolic polarization toward aerobic glycolysis. Such metabolic adaptation enables them to combat the invading pathogens efficiently but also makes them highly nutritionally demanding. Therefore, systemic metabolism has to be adjusted upon macrophage activation to provide them with nutrients and thus support the immune function. That anticipates the involvement of macrophage-derived systemic factors mediating the inter-organ signaling between macrophages and central energy-storing organs. Although it is crucial to coordinate the macrophage cellular metabolism with systemic metabolic changes during the acute phase of bacterial infection, the action of macrophage-derived factors may become maladaptive if chronic or in case of infection by an intracellular pathogen. We hypothesize that insulin resistance evoked by macrophage-derived signaling factors represents an adaptive mechanism for the mobilization of sources and their preferential delivery toward the activated immune system. We consider here the validity of the presented model for mammals and human medicine. The adoption of aerobic glycolysis by bactericidal macrophages as well as the induction of insulin resistance by macrophage-derived factors are conserved between insects and mammals. Chronic insulin resistance is at the base of many human metabolically conditioned diseases such as non-alcoholic steatohepatitis, atherosclerosis, diabetes, and cachexia. Therefore, revealing the original biological relevance of cytokine-induced insulin resistance may help to develop a suitable strategy for treating these frequent diseases. Frontiers Media S.A. 2021-02-15 /pmc/articles/PMC7917182/ /pubmed/33659253 http://dx.doi.org/10.3389/fcell.2021.629238 Text en Copyright © 2021 Bajgar, Krejčová and Doležal. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Bajgar, Adam
Krejčová, Gabriela
Doležal, Tomáš
Polarization of Macrophages in Insects: Opening Gates for Immuno-Metabolic Research
title Polarization of Macrophages in Insects: Opening Gates for Immuno-Metabolic Research
title_full Polarization of Macrophages in Insects: Opening Gates for Immuno-Metabolic Research
title_fullStr Polarization of Macrophages in Insects: Opening Gates for Immuno-Metabolic Research
title_full_unstemmed Polarization of Macrophages in Insects: Opening Gates for Immuno-Metabolic Research
title_short Polarization of Macrophages in Insects: Opening Gates for Immuno-Metabolic Research
title_sort polarization of macrophages in insects: opening gates for immuno-metabolic research
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917182/
https://www.ncbi.nlm.nih.gov/pubmed/33659253
http://dx.doi.org/10.3389/fcell.2021.629238
work_keys_str_mv AT bajgaradam polarizationofmacrophagesininsectsopeninggatesforimmunometabolicresearch
AT krejcovagabriela polarizationofmacrophagesininsectsopeninggatesforimmunometabolicresearch
AT dolezaltomas polarizationofmacrophagesininsectsopeninggatesforimmunometabolicresearch