Lipid droplet formation in leprosy: Toll-like receptor-regulated organelles involved in eicosanoid formation and Mycobacterium leprae pathogenesis

• Published in: Journal of leukocyte biology Vol. 87; no. 3; pp. 371 - 384
• Main Authors: Mattos, Katherine A., D'Avila, Heloisa, Rodrigues, Luciana S., Oliveira, Viviane G. C., Sarno, Euzenir N., Atella, Georgia C., Pereira, Geraldo M., Bozza, Patricia T., Pessolani, Maria Cristina V.
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.03.2010
• Subjects: Animals; Biopsy; Culture Media, Conditioned - pharmacology; Cytoskeleton - drug effects; Cytoskeleton - metabolism; Dinoprostone - biosynthesis; Eicosanoids - biosynthesis; foamy cell; Humans; lepromatous leprosy; Leprosy - metabolism; Leprosy - microbiology; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - microbiology; Leukocytes, Mononuclear - pathology; Lipid Metabolism - drug effects; macrophage; Macrophage Activation - drug effects; Membrane Proteins - metabolism; Mice; mycobacteria; Mycobacterium leprae - drug effects; Mycobacterium leprae - pathogenicity; Organelles - metabolism; Organelles - microbiology; Paracrine Communication - drug effects; Perilipin-2; Phagocytosis - drug effects; prostaglandin E2; Signal Transduction - drug effects; Skin - microbiology; Skin - pathology; Toll-Like Receptor 2 - metabolism; Toll-Like Receptor 6 - metabolism; Toll-Like Receptors - metabolism
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.0609433

Lipid droplets induced by Mycobacterium leprae in macrophages are Toll‐like receptor‐regulated organelles involved in eicosanoid formation and leprosy pathogenesis. A hallmark of LL is the accumulation of Virchow's foamy macrophages. However, the origin and nature of these lipids, as well as their function and contribution to leprosy disease, remain unclear. We herein show that macrophages present in LL dermal lesions are highly positive for ADRP, suggesting that their foamy aspect is at least in part derived from LD (also known as lipid bodies) accumulation induced during ML infection. Indeed, the capacity of ML to induce LD formation was confirmed in vivo via an experimental model of mouse pleurisy and in in vitro studies with human peripheral monocytes and murine peritoneal macrophages. Furthermore, infected cells were shown to propagate LD induction to uninfected, neighboring cells by generating a paracrine signal, for which TLR2 and TLR6 were demonstrated to be essential. However, TLR2 and TLR6 deletions affected LD formation in bacterium‐bearing cells only partially, suggesting the involvement of alternative receptors of the innate immune response besides TLR2/6 for ML recognition by macrophages. Finally, a direct correlation between LD formation and PGE2 production was observed, indicating that ML‐induced LDs constitute intracellular sites for eicosanoid synthesis and that foamy cells may be critical regulators in subverting the immune response in leprosy.