Metabolomic Profile of BALB/c Macrophages Infected with Leishmania amazonensis: Deciphering L-Arginine Metabolism

Autor(es)

Marcia Muxel, Sandra ^{[1, 2]} ; Mamani-Huanca, Maricruz ^[2] ; Aoki, Juliana Ide ^[1] ; Zampieri, Ricardo Andrade ^[1] ; Floeter-Winter, Lucile Maria ^[1] ; Lopez-Gonzalvez, Angeles ^[2] ; Barbas, Coral ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biociencias, Dept Fisiol, BR-05508090 Sao Paulo, SP - Brazil

^[2] Univ CEU San Pablo, Ctr Metabol & Bioanal CEMBIO, Dept Quim & Bioquim, Fac Farm, Campus Monteprincipe, Madrid 28660 - Spain

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 20, n. 24 DEC 2019.
• Citações Web of Science: 0

Resumo

Background: Leishmaniases are neglected tropical diseases that are caused by Leishmania, being endemic worldwide. L-arginine is an essential amino acid that is required for polyamines production on mammal cells. During Leishmania infection of macrophages, L-arginine is used by host and parasite arginase to produce polyamines, leading to parasite survival; or, by nitric oxide synthase 2 to produce nitric oxide leading to parasite killing. Here, we determined the metabolomic profile of BALB/c macrophages that were infected with L. amazonensis wild type or with L. amazonensis arginase knockout, correlating the regulation of L-arginine metabolism from both host and parasite. Methods: The metabolites of infected macrophages were analyzed by capillary electrophoresis coupled with mass spectrometry (CE-MS). The metabolic fingerprints analysis provided the dual profile from the host and parasite. Results: We observed increased levels of proline, glutamic acid, glutamine, L-arginine, ornithine, and putrescine in infected-L. amazonensis wild type macrophages, which indicated that this infection induces the polyamine production. Despite this, we observed reduced levels of ornithine, proline, and trypanothione in infected-L. amazonensis arginase knockout macrophages, indicating that this infection reduces the polyamine production. Conclusions: The metabolome fingerprint indicated that Leishmania infection alters the L-arginine/polyamines/trypanothione metabolism inside the host cell and the parasite arginase impacts on L-arginine metabolism and polyamine production, defining the infection fate. (AU)

• Processo FAPESP: 17/23519-2 - Análise do papel de fatores de transcrição e miRNAs na regulação da expressão gênica em macrófagos murinos infectados por Leishmania amazonenses
• Beneficiário: Stephanie Maia Acuna
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 18/23512-0 - A relação Leishmania-hospedeiro sob a ótica das ‘ômicas’
• Beneficiário: Lucile Maria Floeter-Winter
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 18/24693-9 - Integração dos sinais mediados por fatores de transcrição, long-noncoding RNAs e microRNAs na resposta imune frente a infecção por Leishmania amazonensis
• Beneficiário: Sandra Marcia Muxel
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/03273-6 - Análise de transcriptoma de macrófagos murinos infectados com Leishmania amazonensis: análise de transcritos do parasita e hospedeiro
• Beneficiário: Juliana Ide Aoki
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado