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The impact of cholesteryl ester transfer protein on the progression of cutaneous leishmaniasis.
Batista-Dantas, Francisca Elda; Ozaki, Christiane Yumi; Santana, Kelly Gomes; Nunes, Valéria Sutti; Uscata, Bernardina Amorin; Siess-Portugal, Cinthia; Reis, Luiza Campos; Yamashiro-Kanashiro, Edite H; Tafuri, Wagner Luiz; Duarte-Neto, Amaro Nunes; Sotto, Mirian Nacagami; Goto, Hiro; Cazita, Patrícia Miralda.
  • Batista-Dantas FE; Laboratorio de Lipides (LIM10), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
  • Ozaki CY; Instituto de Medicina Tropical, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
  • Santana KG; Laboratorio de Lipides (LIM10), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
  • Nunes VS; Laboratorio de Lipides (LIM10), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
  • Uscata BA; Instituto de Medicina Tropical, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
  • Siess-Portugal C; Instituto de Medicina Tropical, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
  • Reis LC; Instituto de Medicina Tropical, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
  • Yamashiro-Kanashiro EH; Facultad de Medicina, Universidad Nacional Toribio Rodriguez de Mendoza de Amazonas, Chachapoyas, Peru.
  • Tafuri WL; Instituto de Medicina Tropical, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
  • Duarte-Neto AN; Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
  • Sotto MN; Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Goto H; Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Cazita PM; Instituto de Medicina Tropical, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
Front Immunol ; 15: 1389551, 2024.
Article en En | MEDLINE | ID: mdl-38966642
ABSTRACT

Introduction:

Pathogenesis of cutaneous leishmaniases involves parasite growth, persistent inflammation, and likely participation of lipoproteins (LP). The cholesteryl ester transfer protein (CETP), involved in LP remodeling, has been shown to participate in the inflammatory response and the evolution of infectious conditions.

Methods:

We evaluated the impact of the presence of CETP on infection by Leishmania (L.) amazonensis in an experimental model of cutaneous leishmaniasis using C57BL6/J mice transgenic for human CETP (CETP), having as control their littermates that do not express the protein, wild-type (WT) mice. The progression of the lesion after infection in the footpad was monitored for 12 weeks. Two groups of animals were formed to collect the plantar pad in the 4th and 12th week post-infection.

Results:

The lesion increased from the 3rd week onwards, in both groups, with a gradual decrease from the 10th week onwards in the CETP group compared to the WT group, showing a reduction in parasitism and an improvement in the healing process, a reduction in CD68+ cells, and an increase in CD163+ and CD206, characterizing a population of M2 macrophages. A reduction in ARG1+ cells and an increase in INOS+ cells were observed. During infection, the LP profile showed an increase in triglycerides in the VLDL fraction in the CETP group at 12 weeks. Gene expression revealed a decrease in the CD36 receptor in the CETP group at 12 weeks, correlating with healing and parasite reduction. In vitro, macrophages derived from bone marrow cells from CETP mice showed lower parasite load at 48 h and, a reduction in arginase activity at 4 h accompanied by increased NO production at 4 and 24 h compared to WT macrophages, corroborating the in vivo findings.

Discussion:

The data indicate that the presence of CETP plays an important role in resolving Leishmania (L.) amazonensis infection, reducing parasitism, and modulating the inflammatory response in controlling infection and tissue repair.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Ratones Transgénicos / Leishmaniasis Cutánea / Proteínas de Transferencia de Ésteres de Colesterol / Macrófagos / Ratones Endogámicos C57BL Límite: Animals / Humans Idioma: En Año: 2024 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Ratones Transgénicos / Leishmaniasis Cutánea / Proteínas de Transferencia de Ésteres de Colesterol / Macrófagos / Ratones Endogámicos C57BL Límite: Animals / Humans Idioma: En Año: 2024 Tipo del documento: Article