| Full text | |
| Author(s): |
Zanatta, Jonathan Miguel
;
Acuna, Stephanie Maia
;
Angelo, Yan de Souza
;
Bento, Camilla de Almeida
;
Peron, Jean Pierre Schatzman
;
Stolf, Beatriz Simonsen
;
Muxel, Sandra Marcia
Total Authors: 7
|
| Document type: | Journal article |
| Source: | PLoS One; v. 18, n. 3, p. 25-pg., 2023-03-31. |
| Abstract | |
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) | |
| FAPESP's process: | 17/23519-2 - Analysis of role of miRNAs and transcription factors on the regulation of gene expression of Leishmania amazonensis infected murine macrophages |
| Grantee: | Stephanie Maia Acuna |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 22/00291-4 - Function of long-noncoding RNAs and microRNAs in the immune response and metabolism during Leishmania infection and the interference in the metabolism as new therapeutic strategy |
| Grantee: | Sandra Marcia Muxel |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 18/24693-9 - Integration of signaling mediated by transcription factors, long-noncoding RNAs and microRNAs during immune response agaisnt Leishmania amazonensis infection |
| Grantee: | Sandra Marcia Muxel |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 18/18499-5 - Characterization of homeobox gene Cux1 and its intronic microRNA miR-721 in murine macrophages infected with Leishmania amazonensis |
| Grantee: | Camilla de Almeida Bento |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |
| FAPESP's process: | 19/07089-3 - Influence of L-arginine and polyamines metabolism for transcripts and microRNAs profile in murine macrophages infected with Leishmania amazonensis |
| Grantee: | Jonathan Miguel Zanatta |
| Support Opportunities: | Scholarships in Brazil - Master |