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.
Subject(s)
Cholesterol Ester Transfer Proteins , Leishmaniasis, Cutaneous , Macrophages , Mice, Inbred C57BL , Mice, Transgenic , Animals , Cholesterol Ester Transfer Proteins/genetics , Cholesterol Ester Transfer Proteins/metabolism , Leishmaniasis, Cutaneous/immunology , Leishmaniasis, Cutaneous/parasitology , Leishmaniasis, Cutaneous/metabolism , Mice , Macrophages/immunology , Macrophages/metabolism , Macrophages/parasitology , Humans , Disease Progression , Disease Models, AnimalABSTRACT
Escherichia coli enterotoxigênica (ETEC) é responsavél por pelo menos, 400 milhões de episódios de diarreía aguda e 700.000 mortes de crianças com menos de cinco anos de idade anualmente, sendo considerada também a principal causa da " dairréia dos viajantes", que afetam turistas em trânsito de áreas endêmicas. O diagnóstico da infecção por ETEC é baseada na detecção dos seus principais fatores de virulência as toxinas termo-lábil (LT) e termo-estável (ST) atráves de métodos de biologia molecular ou imunossorológicos apresentam vantagens, como alta especificidade e sensibilidade, além da fácil preparação das amostras e execução dos testes. Avanços na tecnologia dos anticorpos recombinantes permitiram a obtenção de moléculas com baixo custo, afinidades e especificidades desejáveis... .
Enterotoxigenic Escherichia coli (ETEC) are responsible for at least 400 mllion acute diarrhea episodes and 700.000 childhood deaths under age of five per year. ETEC is also a prevalent cause of traveler´s diarrhea, wich affects tourists who visit endemic areas. Heat-labile (LT) and heat - stable (ST) toxins are the main ETEC virulence factors, and diagnosis of infection is based on their detection by molecular biology or immunoserological methods. Immunoserological assay has some advantages when using specif antibodies, including high specific and sensivity with convenient procedures for sample preparation and assay execution. Advances in antibody biotecnology provide alternatives to obtain low cost antibodies with desirable affinities... .
