CD14 regulates the metabolomic profiles of distinct macrophage subsets under steady and activated states

Autor(es)

de Macedo, Luana Henrique ; Souza, Camila Oliveira Silva ; Gardinassi, Luiz Gustavo ; Faccioli, Lucia Helena

• Tipo de documento: Artigo Científico
• Fonte: Immunobiology; v. 227, n. 2, p. 10-pg., 2022-02-19.

Resumo

Macrophages play pivotal roles during homeostasis and inflammation. They sense exogenous and endogenous molecular patterns via surface and intracellular receptors, which trigger innate immune responses. CD14 is a co-receptor for lipopolysaccharide (LPS), but also drives macrophage responses to Tityus serrulatus scorpion venom (TsV). Cellular activation is tightly coupled with metabolism that sustain their polarization and generate anti-microbial and signaling molecules. Macrophage's origin and nature of stimulus are critical for their responses, but whether these factors impact macrophage metabolism is unknown. Moreover, the regulation of intracellular metabolism by CD14 has not been assessed. Using an untargeted metabolomics approach, we determined the longitudinal metabolic responses of peritoneal (PMs) and bone marrow derived macrophages (BMDMs) stimu-lated with LPS and TsV for 12 h. These data revealed alterations on the relative levels of several metabolites and pathways related to amino acids, nucleotides, lipids, and vitamins. Our data suggest activation of selenoamino acid metabolism and increased abundance of selenomethionine in both cell subsets stimulated with LPS. Moreover, the results suggest a differential activity of vitamin B3 metabolism pathway in response to TsV stimulus, with differences on regulation of the relative levels of nicotinamide mononucleotide and deamino-NAD+. CD14 deficiency affects the metabolome of both cell subsets at steady state. Moreover, CD14 was required for arginine consumption in PMs stimulated with LPS, but not TsV or by BMDMs stimulated by both stimuli. Importantly, the data suggest that CD14 mediates the accumulation of lipids in both macrophage subsets stimulated with LPS, providing insights into the potential role of CD14 for the development of metabolic dis-eases. We conclude that macrophages acquire a spectrum of metabolic profiles that depend on the origin of these cells, the nature of the stimuli and signaling by innate immune receptors. (AU)

• Processo FAPESP: 14/07125-6 - Novos aspectos funcionais dos eicosanóides
• Beneficiário: Lúcia Helena Faccioli
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 18/10929-0 - O papel do receptor CD14 na regulação metabólica de macrófagos estimulados com o veneno do escorpião Tityus serrulatus
• Beneficiário: Luana Henrique de Macedo
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 15/00658-1 - Novos aspectos funcionais dos eicosanóides
• Beneficiário: Lúcia Helena Faccioli
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 18/22667-0 - Papel do CD18 para geração e plasticidade de monócitos durante a infecção por Schistossoma mansoni
• Beneficiário: Camila de Oliveira Silva e Souza
• Modalidade de apoio: Bolsas no Brasil - Doutorado