PMID- 35189540 OWN - NLM STAT- MEDLINE DCOM- 20220502 LR - 20220502 IS - 1878-3279 (Electronic) IS - 0171-2985 (Linking) VI - 227 IP - 2 DP - 2022 Mar TI - CD14 regulates the metabolomic profiles of distinct macrophage subsets under steady and activated states. PG - 152191 LID - S0171-2985(22)00017-1 [pii] LID - 10.1016/j.imbio.2022.152191 [doi] AB - 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 antimicrobial 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) stimulated 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 diseases. 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. CI - Copyright (c) 2022 Elsevier GmbH. All rights reserved. FAU - de Macedo, Luana Henrique AU - de Macedo LH AD - Departamento de Analises Clinicas, Toxicologicas e Bromatologicas, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, SP, Brazil. FAU - Souza, Camila Oliveira Silva AU - Souza COS AD - Departamento de Analises Clinicas, Toxicologicas e Bromatologicas, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, SP, Brazil. FAU - Gardinassi, Luiz Gustavo AU - Gardinassi LG AD - Departamento de Analises Clinicas, Toxicologicas e Bromatologicas, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, SP, Brazil; Departamento de Biociencias e Tecnologia, Instituto de Patologia Tropical e Saude Publica, Universidade Federal de Goias, Goiania, GO, Brazil. Electronic address: luizgardinassi@ufg.br. FAU - Faccioli, Lucia Helena AU - Faccioli LH AD - Departamento de Analises Clinicas, Toxicologicas e Bromatologicas, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, SP, Brazil. Electronic address: faccioli@fcfrp.usp.br. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220217 PL - Netherlands TA - Immunobiology JT - Immunobiology JID - 8002742 RN - 0 (Lipopolysaccharide Receptors) RN - 0 (Lipopolysaccharides) RN - 0 (Scorpion Venoms) SB - IM MH - Lipopolysaccharide Receptors/metabolism MH - *Lipopolysaccharides/metabolism MH - Macrophages MH - Metabolomics MH - *Scorpion Venoms/metabolism MH - Signal Transduction OTO - NOTNLM OT - CD14 OT - Homeostasis OT - Inflammation OT - Macrophages OT - Metabolomics EDAT- 2022/02/22 06:00 MHDA- 2022/05/03 06:00 CRDT- 2022/02/21 20:13 PHST- 2021/10/16 00:00 [received] PHST- 2022/01/28 00:00 [revised] PHST- 2022/02/14 00:00 [accepted] PHST- 2022/02/22 06:00 [pubmed] PHST- 2022/05/03 06:00 [medline] PHST- 2022/02/21 20:13 [entrez] AID - S0171-2985(22)00017-1 [pii] AID - 10.1016/j.imbio.2022.152191 [doi] PST - ppublish SO - Immunobiology. 2022 Mar;227(2):152191. doi: 10.1016/j.imbio.2022.152191. Epub 2022 Feb 17.