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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 <jats:italic>Leishmania<\/jats:italic> survival. Here, we investigate the effect of supplementation with L-arginine and polyamines in infection of murine BALB\/c macrophages by <jats:italic>L<\/jats:italic>. <jats:italic>amazonensis<\/jats:italic> 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 (<jats:italic>Nos<\/jats:italic>2) gene expression without changes in NO production. Putrescine supplementation increased transcript levels of polyamine metabolism-related genes <jats:italic>Arg<\/jats:italic>2, ornithine decarboxylase <jats:italic>(Odc1)<\/jats:italic>, Spermidine synthase (<jats:italic>SpdS)<\/jats:italic>, and Spermine synthase (<jats:italic>SpmS<\/jats:italic>), but reduced <jats:italic>Arg1<\/jats:italic> in <jats:italic>L<\/jats:italic>. <jats:italic>amazonensis<\/jats:italic> infected macrophages, while spermidine and spermine promoted opposite effects. Putrescine increased <jats:italic>Nos2<\/jats:italic> 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 <jats:italic>Il-1b<\/jats:italic> during infection, and L-arginine or L-arginine plus putrescine increased <jats:italic>Mcp1<\/jats:italic> 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 <jats:italic>L<\/jats:italic>. <jats:italic>amazonensis<\/jats:italic>.<\/jats:p>","DOI":"10.1371\/journal.pone.0283696","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T17:44:08Z","timestamp":1680284648000},"page":"e0283696","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Putrescine supplementation shifts macrophage L-arginine metabolism related-genes reducing Leishmania amazonensis infection"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8367-9546","authenticated-orcid":true,"given":"Jonathan Miguel","family":"Zanatta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie Maia","family":"Acu\u00f1a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7133-2569","authenticated-orcid":true,"given":"Yan","family":"de Souza Angelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"de Almeida Bento","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Pierre Schatzman","family":"Peron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz Simonsen","family":"Stolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0118-5361","authenticated-orcid":true,"given":"Sandra Marcia","family":"Muxel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,3,31]]},"reference":[{"key":"pone.0283696.ref001","first-page":"1","article-title":"Mammalian Polyamine Metabolism and Function Anthony","volume":"23","author":"AE Pegg","year":"2009","journal-title":"Bone"},{"key":"pone.0283696.ref002","doi-asserted-by":"crossref","first-page":"E751","DOI":"10.1073\/pnas.1614958114","article-title":"Ornithine decarboxylase regulates M1 macrophage activation and mucosal inflammation via histone modifications","volume":"114","author":"DM Hardbower","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0283696.ref003","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1007\/s00726-013-1550-9","article-title":"Chromatin remodeling by polyamines and polyamine analogs","volume":"46","author":"A Pasini","year":"2014","journal-title":"Amino 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