25º Congresso Brasileiro de Microbiologia
ResumoID:2082-1


Área: Micobacteriologa ( Divisão C )

LIPID BODY BIOGENESIS MEDIATED BY MYCOBACTERIUM LEPRAE IN SCHWANN CELLS IS DEPENDENT ON BACTERIAL VIABILITY

Katherine Antunes de Mattos (LAMICEL-IOC); Viviane G. C. Oliveira (LAMICEL-IOC); Luciana Silva Rodrigues (LAMICEL-IOC); Heloisa D'avila (LIMUNOFAR-IOC); Flavio Alves Lara (LAMICEL-IOC); Euzenir Nunes Sarno (LAHAN); Patricia Torres Bozza (LIMUNOFAR-IOC); Maria Cristina Vidal Pessolani (LAMICEL-IOC)

Resumo

The predilection of Schwann cells (SCs) by Mycobacterium leprae (ML) represents a unique feature in leprosy. The frequent association of large numbers of ML with foamy degeneration emphasizes the importance of lipids in the biology of ML infection and suggests possible strategies to combat nerve damage. The origin and nature of these lipids, as well as their function and contribution to leprosy disease remain unclear.  In this study, we analyzed the mechanism of lipid body (LB) organelle biogenesis by ML in SCs. Firstly, an immunohistochemistry analysis of nerves from lepromatous leprosy patients showed SCs highly positive for both ML and adipophilin (ADRP), a marker of LB, suggesting that their foamy aspect is at least in part derived from LB accumulation induced during infection. Moreover, bacterial globis were completely enveloped by ADRP, suggesting a recruitment process of LB by ML. The capacity of ML to induce LB formation was confirmed by in vitro studies with human and murine SCs using microscopy and FACS analysis.  Our observations indicated that ML-LB induction occurs in a time and dose-dependent manner and requires the uptake of live bacteria. LB biogenesis was also inhibited by microtubules and actin-disrupting drugs confirming its dependence on cytoskeleton. In addition, only ML, but not M. smegmatis or BCG was able to induce LB in SCs. Finally, a role for TLR2 and 6 in pathogen recognition and signaling to form LB was investigated. TLR6 but not TLR2 depletion affected LB biogenesis. Interestingly, a concomitant reduction of live ML within TLR6-/- cells was observed, confirming the requirement of bacterial internalization to modulate the lipid metabolism in SCs. Altogether, our data demonstrate the capacity of  ML to induce BL formation in SC, being this process dependent on bacterial viability and regulated by receptors TLR. These findings open the possibility of interfering with ML ability to modulate host lipid metabolism, which may contribute to bacterial survival and subsequently leprosy pathogenesis.

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