Dados do Trabalho

Título

The role of FABP4 in murine cutaneous leishmaniasis caused by L. amazonensis

Introdução

Leishmaniasis is a disease caused by Leishmania spp. for which the current chemotherapy presents high toxicity and usually requires parenteral administration. Thus, studying the mechanisms of infection and nutrient uptake by the parasite may allow the search for new therapeutic targets.In Brazil, one of the main species causing cutaneous leishmaniasis is L. amazonensis and it is known that during the infection, amastigotes divide into the parasitophorous vacuoles of the host cell (macrophages), where the parasite acquires nutrients such as fatty acids. In the macrophage, fatty acids are transported by FABP4, and its transcript is increased in Leishmania-infected macrophages.

Objetivo (s)

In this scenario, the aim was to evaluate the influence of FABP4 on infections with L. amazonensis.

Material e Métodos

For this, macrophages from fapb4-/- and WT C57/BL6 were obtained to evaluate L. amazonensis infections at MOI=2. Indirect immunofluorescence assays were performed, showing higher FABP4 accumulation in infected WT cells. Also, there was a reduction in the infection rates after 1 and 48h for the knockout group. For the in vivo assays, WT and fabp4-/- mice were infected with 1x106 amastigotes of L. amazonensis in the left hind footpad. After 9 weeks, blood was collected from the animals and parasite burden quantification was performed by the limiting dilution method. Besides, total RNA was collected from the lesion site.

Resultados e Conclusão

Our results pointed out that fabp4-/- mice presented reduced lesions up to the 6th week, and an increase after this period when compared to the WT group. In addition, there is a proliferation in the parasite burden of fabp4-/- animals. From the blood serum samples, an increase in total cholesterol was observed in the pool of infected fabp4-/- mice, while triglycerides levels decreased versus WT mice. RT-PCR analyses showed a significant increase in cd36 transcripts that encode a membrane protein responsible for the entry of fatty acids into the cell. Accordingly, our data indicate a modulation of FABP4 pathway for fatty acid acquisition during murine infection by L. amazonensis. In its absence, the infection progresses more severely, showing a relevant function in the control of long-term lesion progression. Our data will pave the way for the identification of important targets related to parasite maintenance and to a better understanding of the pathogenesis and evolution of cutaneous leishmaniasis.

Palavras-chave

Leishmania, infection, FABP4

Agradecimentos

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