Polyamines regulate the expression of genes related to its metabolism and resistance to infection of macrophages with Leishmania amazonensis

Author(s)

Jonathan Miguel Zanatta

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB)
• Defense date: 2022-08-12

Examining board members

Sandra Marcia Muxel; Fernando Ribeiro Gomes; Maria Regina D'Imperio Lima; Nilmar Sílvio Moretti

• Advisor: Sandra Marcia Muxel

Abstract

Macrophages are phagocytic cells of the immune system and represent the first barrier against infection with Leishmania. Leishmania is a protozoan that causes leishmaniasis, a disease that presents clinical manifestations classified as cutaneous, mucocutaneous and visceral leishmaniasis. In the infection context, the parasite can modulate macrophage gene expression affecting microbicidal activity and immune response to the parasite. The metabolization of L-arginine in polyamines (putrescine, spermidine, and spermine) harmful to the nitric oxide (NO) production favoring Leishmania infection. Polyamines are essential for protein and macromolecules synthesis in cells, and cell proliferation and differentiation. In the present study, we evaluated how the availability of L-arginine and polyamines affected the expression of genes related to their metabolism in macrophages of BALB/c mice infected with Leishmania amazonensis and susceptibility to infection. L-arginine deprivation in macrophages during infection with L. amazonensis increased Nos2 expression, but did not induce NO production. However, L-arginine supplementation did not alter the expression of genes related to polyamines transport and biosynthesis. Supplementation with L-arginine and putrescine increased the expression of arginase 2 (Arg2) in infected-macrophages in relation to uninfected macrophages, while the supplementation with spermidine or spermine reduced the expression of Arg2. Supplementation with L-arginine and spermine increased the expression of spermidine synthase (SpdS) in infected macrophages compared to uninfected ones. Putrescine supplementation increased Nos2 expression, but did not increase NO production during infection. Meanwhile, the spermine supplementation of macrophages during infection increased the frequency of NO-producing cells. The Slc3a2/Slc7a5 genes that compose a heterodimer of polyamine transport were modulated. Slc3a2 expression increased in macrophages supplemented with putrescine or L-arginine and spermidine during infection and Slc7a5 increased in spermidine or spermine supplementation during infection. The putrescine supplementation of macrophages during infection increased monocyte chemoattractant protein (Mcp1) gene expression. The infection analysis showed that supplementation with putrescine, L-arginine plus spermidine, or L-arginine plus spermine reduced the percentage of infected macrophage compared to L-arginine supplementation condition. Our data suggest that the polyamines regulate the expression of genes related to their transport and metabolism macrophages infected with L. amazonensis. (AU)

• 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