25º Congresso Brasileiro de Microbiologia

25º Congresso Brasileiro de Microbiologia

ResumoID:643-1

Área: Micobacteriologa ( Divisão C )

MYCOBACTERIUM LEPRAE INDUCES THE UPTAKE OF LDL-CHOLESTEROL BY SCHWANN CELLS

Katherine Antunes de Mattos (FioCruz); Julio Jablonski Amaral (FioCruz); Viviane Gonçalves Carneiro de Oliveira (FioCruz); Georgia Correa Atella (UFRJ); Milton Ozório Moraes (FioCruz); Anna Beatriz Robottom Ferreira (FioCruz); Alejandra Nóbrega Martinez (FioCruz); Maria Cristina Vidal Pessolani (FioCruz)

Resumo

Mycobacterium leprae (ML), the leprosy bacillus, infects and multiplies mainly inside Schwann cells (SCs) of the peripheral nerves and macrophages and is thought to be the mycobacterium most dependent on host metabolic pathways, including host-derived lipids. Indeed, a very frequent observation in lepromatous leprosy lesions is the presence of foamy cells containing large amounts of bacilli and lipid. Reinforcing the hypothesis that ML modulates host cell lipid metabolism, in a very recent study we were able to demonstrate that live but not dead ML induces the formation of lipid bodies in CS. In the present work we further analyze lipid regulation in ML infected SCs focusing on cholesterol metabolism. Cholesterol is the major sterol component of eukariotic cells and it has been shown to be essential for the internalization of mycobacteria by macrophages. Firstly we analyzed the internalization of LDL-cholesterol by SC infected with ML. Human primary SC were infected with ML for 48 h and then labeled with Bodipy-LDL-cholesterol for additional 2 h. Cells were washed with PBS, fixed and LDL-Cholesterol uptake was monitored by fluorescence microscopy and FACS analysis. Our results showed that live but not dead ML induced internalization of LDL-Cholesterol. Moreover, this increase was seen to be dependent on the phagocytosis of ML by SC, since it was observed only in infected SC, while ML-negative cells were not able to incorporate more cholesterol. Currently we are investigating the capacity of ML to regulate the expression of a group of proteins involved in cholesterol metabolism. A preliminary microarray data indicated that two of these proteins, the low-density lipoprotein receptor-related protein-1 (LRP-1) and the sterol regulatory element binding protein-1 (SREBP-1) are upregulated by ML in SCs at the transcriptional level. The expression of these proteins has also been measured by FACS and microscopy analysis and initial results confirm the microarray data. Taken together, these results suggest that ML induces the uptake of LDL-cholesterol by SC, probably by modulating the expression of proteins related to the lipoprotein metabolism, favoring bacterial survival and persistence in the host.

Palavras-chave: Mycobacterium leprae, LDL-cholesterol, Schwann cells, Lipid methabolism

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