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TLR6-driven lipid droplets in Mycobacterium leprae-infected Schwann cells: immunoinflammatory platforms associated with bacterial persistence.
J Immunol. 2011 Sep 01; 187(5):2548-58.JI

Abstract

The mechanisms responsible for nerve injury in leprosy need further elucidation. We recently demonstrated that the foamy phenotype of Mycobacterium leprae-infected Schwann cells (SCs) observed in nerves of multibacillary patients results from the capacity of M. leprae to induce and recruit lipid droplets (LDs; also known as lipid bodies) to bacterial-containing phagosomes. In this study, we analyzed the parameters that govern LD biogenesis by M. leprae in SCs and how this contributes to the innate immune response elicited by M. leprae. Our observations indicated that LD formation requires the uptake of live bacteria and depends on host cell cytoskeleton rearrangement and vesicular trafficking. TLR6 deletion, but not TLR2, completely abolished the induction of LDs by M. leprae, as well as inhibited the bacterial uptake in SCs. M. leprae-induced LD biogenesis correlated with increased PGE(2) and IL-10 secretion, as well as reduced IL-12 and NO production in M. leprae-infected SCs. Analysis of nerves from lepromatous leprosy patients showed colocalization of M. leprae, LDs, and cyclooxygenase-2 in SCs, indicating that LDs are sites for PGE(2) synthesis in vivo. LD biogenesis Inhibition by the fatty acid synthase inhibitor C-75 abolished the effect of M. leprae on SC production of immunoinflammatory mediators and enhanced the mycobacterial-killing ability of SCs. Altogether, our data indicated a critical role for TLR6-dependent signaling in M. leprae-SC interactions, favoring phagocytosis and subsequent signaling for induction of LD biogenesis in infected cells. Moreover, our observations reinforced the role of LDs favoring mycobacterial survival and persistence in the nerve. These findings give further support to a critical role for LDs in M. leprae pathogenesis in the nerve.

Authors+Show Affiliations

Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ 21045-900, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21813774

Citation

Mattos, Katherine A., et al. "TLR6-driven Lipid Droplets in Mycobacterium Leprae-infected Schwann Cells: Immunoinflammatory Platforms Associated With Bacterial Persistence." Journal of Immunology (Baltimore, Md. : 1950), vol. 187, no. 5, 2011, pp. 2548-58.
Mattos KA, Oliveira VG, D'Avila H, et al. TLR6-driven lipid droplets in Mycobacterium leprae-infected Schwann cells: immunoinflammatory platforms associated with bacterial persistence. J Immunol. 2011;187(5):2548-58.
Mattos, K. A., Oliveira, V. G., D'Avila, H., Rodrigues, L. S., Pinheiro, R. O., Sarno, E. N., Pessolani, M. C., & Bozza, P. T. (2011). TLR6-driven lipid droplets in Mycobacterium leprae-infected Schwann cells: immunoinflammatory platforms associated with bacterial persistence. Journal of Immunology (Baltimore, Md. : 1950), 187(5), 2548-58. https://doi.org/10.4049/jimmunol.1101344
Mattos KA, et al. TLR6-driven Lipid Droplets in Mycobacterium Leprae-infected Schwann Cells: Immunoinflammatory Platforms Associated With Bacterial Persistence. J Immunol. 2011 Sep 1;187(5):2548-58. PubMed PMID: 21813774.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TLR6-driven lipid droplets in Mycobacterium leprae-infected Schwann cells: immunoinflammatory platforms associated with bacterial persistence. AU - Mattos,Katherine A, AU - Oliveira,Viviane G C, AU - D'Avila,Heloisa, AU - Rodrigues,Luciana S, AU - Pinheiro,Roberta O, AU - Sarno,Euzenir N, AU - Pessolani,Maria Cristina V, AU - Bozza,Patricia T, Y1 - 2011/08/03/ PY - 2011/8/5/entrez PY - 2011/8/5/pubmed PY - 2011/10/20/medline SP - 2548 EP - 58 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 187 IS - 5 N2 - The mechanisms responsible for nerve injury in leprosy need further elucidation. We recently demonstrated that the foamy phenotype of Mycobacterium leprae-infected Schwann cells (SCs) observed in nerves of multibacillary patients results from the capacity of M. leprae to induce and recruit lipid droplets (LDs; also known as lipid bodies) to bacterial-containing phagosomes. In this study, we analyzed the parameters that govern LD biogenesis by M. leprae in SCs and how this contributes to the innate immune response elicited by M. leprae. Our observations indicated that LD formation requires the uptake of live bacteria and depends on host cell cytoskeleton rearrangement and vesicular trafficking. TLR6 deletion, but not TLR2, completely abolished the induction of LDs by M. leprae, as well as inhibited the bacterial uptake in SCs. M. leprae-induced LD biogenesis correlated with increased PGE(2) and IL-10 secretion, as well as reduced IL-12 and NO production in M. leprae-infected SCs. Analysis of nerves from lepromatous leprosy patients showed colocalization of M. leprae, LDs, and cyclooxygenase-2 in SCs, indicating that LDs are sites for PGE(2) synthesis in vivo. LD biogenesis Inhibition by the fatty acid synthase inhibitor C-75 abolished the effect of M. leprae on SC production of immunoinflammatory mediators and enhanced the mycobacterial-killing ability of SCs. Altogether, our data indicated a critical role for TLR6-dependent signaling in M. leprae-SC interactions, favoring phagocytosis and subsequent signaling for induction of LD biogenesis in infected cells. Moreover, our observations reinforced the role of LDs favoring mycobacterial survival and persistence in the nerve. These findings give further support to a critical role for LDs in M. leprae pathogenesis in the nerve. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/21813774/TLR6_driven_lipid_droplets_in_Mycobacterium_leprae_infected_Schwann_cells:_immunoinflammatory_platforms_associated_with_bacterial_persistence_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=21813774 DB - PRIME DP - Unbound Medicine ER -