Advanced search
Start date

Immunometabolic adaptation of tissue resident macrophages in health and disease

Grant number: 20/16030-0
Support Opportunities:Research Projects - Thematic Grants
Duration: April 01, 2022 - March 31, 2027
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Pedro Manoel Mendes de Moraes Vieira
Grantee:Pedro Manoel Mendes de Moraes Vieira
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated researchers: Alan Saghatelian ; Ana de Medeiros Arnt ; André Ricardo de Lima Damasio ; Daniel Martins-de-Souza ; Dionicio Siegel ; Jean Pierre Schatzmann Peron ; Luiz Osório Silveira Leiria ; Marcelo Alves da Silva Mori ; Mariana Boroni ; Niels Olsen Saraiva Câmara ; Peter J. Murray
Associated grant(s):22/13587-9 - Microbiota-derived metabolites in the regulation of the gut immune system and systemic metabolism in aging mice, AP.R SPRINT
22/04576-3 - EMU awarded in process 2020/16030-0: 96-well metabolic analyzer seahorse XFe96, AP.EMU
Associated scholarship(s):23/05714-3 - Study of the role of gluconeogenesis in inflammatory macrophages, BP.MS
21/00187-0 - The role of macrophage mitochondrial dynamics in the regulation of browning., BP.DR
23/05404-4 - Technical support for cell culture and molecular biology, BP.TT
+ associated scholarships 22/16083-1 - Study on the role of T-bet in macrophages in the regulation of obesity-induced metabolic syndrome, BP.DR
22/13610-0 - Study of the modulation of HIF-1alpha and NF-kB on macrophage glucose metabolism and pro-inflammatory profile, BP.MS
23/01856-8 - Study of the mitophagic pathway regulation in macrophages by HIF-1a, BP.DD
22/15815-9 - Investigation of mitochondrial dynamics on macrophage polarization in the tumor microenvironment, BP.IC
22/05429-4 - High-resolution profiling of adipose tissue macrophages, BP.PD
20/09535-8 - Modulation of mitochondrial dynamics as an approach for macrophage repolarization in cancer treatment, BP.PD
20/02573-1 - Effects of Aryl Hydrocarbon Receptor (AHR) modulation on the activation and metabolism of macrophages in lean and obese mice, BP.PD - associated scholarships


The growing interest in Immunometabolism is fueled by the global obesity epidemic and obesity-induced inflammation is a risk factor for several chronic pathologies and diseases. The field of Immunometabolism is the new frontier for Immunology as it integrates the historically distinct disciplines of Metabolism and Immunology. Studies on macrophage metabolic adaptation largely relies in the investigation of bone marrow derived macrophages and a major gap exists between metabolic regulation of in vitro generated bone marrow macrophages and tissue resident macrophages. The biochemical activities occurring in macrophages are linked to its function and ultimately to mitochondria morphology. Systemic and tissue-derived cues shape macrophage metabolism and mitochondria morphology through fission/fusion events, which orchestrates the overall cellular metabolism and how mitochondria function. Macrophages must rapidly alter their metabolism according to extrinsic cues such as cytokines and microbial products, to acquire different phenotypes and functional states necessary for the downstream function. Activated macrophages have increased metabolic demands closely linked to mitochondria bioenergetics. However, in macrophages, almost nothing is known about the metabolic regulation of these cells within specific tissues, such as in the adipose tissue or brain (microglia) both under physiologic and pathologic circumstances. In general, the proposal is centered on the hypothesis that cellular metabolic pathways (glycolysis, lipolysis, lipogenesis, biosynthesis and degradation of amino acids, transport of molecules by SLCs, among others) and tissue-derived factors orchestrate the function of tissue resident macrophages. The overall goal is to determine how tissue resident macrophages adapt their metabolism to fulfill their function during health and disease. For this, we will (i) evaluate how mitochondria dynamics regulates macrophage phenotype and function, (ii) investigate the role of key transcription factors such as AHR and HIF-1±, and also the metabolic sensor mTOR, in the regulation of macrophage metabolism, (iii) determine the spectrum of macrophage phenotypes in the adipose tissue by single cell RNA sequencing, (iv) describe the SLCs involved in macrophage response against infectious agents and (v) analyze the involvement of tissue derived factors, such as leptin and FAHFAs in the phenotype and function of macrophages and their importance for adipose tissue inflammation-induced insulin resistance and microglia activation during obesity. This unpaved area of research will bring new insights into the field of immunometabolism to further our knowledge into the immunometabolic regulation of tissue resident macrophages. This proposal offers new insights into how macrophage metabolic adaptation regulates the outcomes of auto-inflammatory, metabolic and infectious diseases with great potential for patient wellbeing, as macrophage metabolism is linked to virtually every acute and chronic disease. Findings from this proposal could lead to the discovery of still unknown pathways and possibly novel treatments for inflammatory diseases. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
Articles published in other media outlets (0 total):
More itemsLess items

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DAVANZO, GUSTAVO GASTAO; CASTRO, GISELE; MONTEIRO, LAUAR DE BRITO; CASTELUCCI, BIANCA GAZIERI; JACCOMO, VITOR HUGO; SILVA, FELIPE CORREA DA; MARQUES, ANA MARIA; FRANCELIN, CAROLINA; CAMPOS, BRUNA BUENO DE; AGUIAR, CRISTHIANE FAVERO DE; et al. Obesity increases blood-brain barrier permeability and aggravates the mouse model of multiple sclerosis. MULTIPLE SCLEROSIS AND RELATED DISORDERS, v. 72, p. 7-pg., . (20/16030-0, 15/10107-2, 15/15626-8, 19/25973-8, 16/18031-8)
MONTEIRO, LAUAR DE BRITO; PRODONOFF, JULIANA SILVEIRA; DE AGUIAR, CRISTHIANE FAVERO; CORREA-DA-SILVA, FELIPE; CASTOLDI, ANGELA; BAKKER, NIKKI VAN TEIJLINGEN; DAVANZO, GUSTAVO GASTAO; CASTELUCCI, BIANCA; PEREIRA, JESSICA APARECIDA DA SILVA; CURTIS, JONATHAN; et al. Leptin Signaling Suppression in Macrophages Improves Immunometabolic Outcomes in Obesity. Diabetes, v. 71, n. 7, p. 16-pg., . (13/07607-8, 19/06372-3, 18/19338-5, 16/23328-0, 19/25973-8, 20/16030-0, 19/19435-3)
DOS REIS, LARISSA MENEZES; BERCOT, MARCELO RODRIGUES; CASTELUCCI, BIANCA GAZIERI; MARTINS, ANA JULIA ESTUMANO; CASTRO, GISELE; MORAES-VIEIRA, PEDRO M. M.. Immunometabolic Signature during Respiratory Viral Infection: A Potential Target for Host-Directed Therapies. Viruses-Basel, v. 15, n. 2, p. 32-pg., . (20/09535-8, 19/25973-8, 20/16030-0, 21/01147-1)

Please report errors in scientific publications list by writing to: