Putrescine supplementation shifts macrophage L-arginine metabolism related-genes reducing Leishmania amazonensis infection

Autor(es)

Zanatta, Jonathan Miguel ; Acuna, Stephanie Maia ; Angelo, Yan de Souza ; Bento, Camilla de Almeida ; Peron, Jean Pierre Schatzman ; Stolf, Beatriz Simonsen ; Muxel, Sandra Marcia

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 18, n. 3, p. 25-pg., 2023-03-31.

Resumo

Leishmania is a protozoan that causes leishmaniasis, a neglected tropical disease with clinical manifestations classified as cutaneous, mucocutaneous, and visceral leishmaniasis. In the infection context, the parasite can modulate macrophage gene expression affecting the microbicidal activity and immune response. The metabolism of L-arginine into polyamines putrescine, spermidine, and spermine reduces nitric oxide (NO) production, favoring Leishmania survival. Here, we investigate the effect of supplementation with L-arginine and polyamines in infection of murine BALB/c macrophages by L. amazonensis and in the transcriptional regulation of genes involved in arginine metabolism and proinflammatory response. We showed a reduction in the percentage of infected macrophages upon putrescine supplementation compared to L-arginine, spermidine, and spermine supplementation. Unexpectedly, deprivation of L-arginine increased nitric oxide synthase (Nos2) gene expression without changes in NO production. Putrescine supplementation increased transcript levels of polyamine metabolism-related genes Arg2, ornithine decarboxylase (Odc1), Spermidine synthase (SpdS), and Spermine synthase (SpmS), but reduced Arg1 in L. amazonensis infected macrophages, while spermidine and spermine promoted opposite effects. Putrescine increased Nos2 expression without leading to NO production, while L-arginine plus spermine led to NO production in uninfected macrophages, suggesting that polyamines can induce NO production. Besides, L-arginine supplementation reduced Il-1b during infection, and L-arginine or L-arginine plus putrescine increased Mcp1 at 24h of infection, suggesting that polyamines availability can interfere with cytokine/chemokine production. Our data showed that putrescine shifts L-arginine-metabolism related-genes on BALB/c macrophages and affects infection by L. amazonensis. (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: 22/00291-4 - Função de long-noncoding RNAs e microRNAs na resposta imune e metabolismo na infecção por Leishmania e uso de interferência metabólica como estratégia terapêutica
• Beneficiário: Sandra Marcia Muxel
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• 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: 18/18499-5 - Estabelecimento de função do gene homeótico Cux1 e de seu microRNA intrônico miR-721 de macrófagos murinos infectados com Leishmania amazonensis
• Beneficiário: Camilla de Almeida Bento
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 19/07089-3 - Influência do metabolismo de L-arginina e poliaminas no perfil de transcritos e microRNAs em macrófagos murinos infectados com Leishmania amazonensis
• Beneficiário: Jonathan Miguel Zanatta
• Modalidade de apoio: Bolsas no Brasil - Mestrado