In:
PLOS ONE, Public Library of Science (PLoS), Vol. 18, No. 3 ( 2023-3-31), p. e0283696-
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 ( Nos 2) gene expression without changes in NO production. Putrescine supplementation increased transcript levels of polyamine metabolism-related genes Arg 2, 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 .
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0283696
DOI:
10.1371/journal.pone.0283696.g001
DOI:
10.1371/journal.pone.0283696.g002
DOI:
10.1371/journal.pone.0283696.g003
DOI:
10.1371/journal.pone.0283696.g004
DOI:
10.1371/journal.pone.0283696.g005
DOI:
10.1371/journal.pone.0283696.g006
DOI:
10.1371/journal.pone.0283696.t001
DOI:
10.1371/journal.pone.0283696.s001
DOI:
10.1371/journal.pone.0283696.s002
DOI:
10.1371/journal.pone.0283696.s003
DOI:
10.1371/journal.pone.0283696.s004
DOI:
10.1371/journal.pone.0283696.s005
DOI:
10.1371/journal.pone.0283696.s006
DOI:
10.1371/journal.pone.0283696.s007
DOI:
10.1371/journal.pone.0283696.s008
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2267670-3
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