Laboratórios de Microbiologia Celular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
J Leukoc Biol. 2010 Mar;87(3):371-84. doi: 10.1189/jlb.0609433. Epub 2009 Dec 1.
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 PGE(2) 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.
麻风病的一个标志是魏尔啸泡沫细胞的积累。然而，这些脂质的来源和性质，以及它们的功能和对麻风病的贡献，仍然不清楚。我们在此表明，麻风病皮肤损伤中的巨噬细胞对 ADRP 呈高度阳性，这表明其泡沫状外观至少部分来源于 ML 感染期间诱导的 LD（也称为脂滴）积累。事实上，通过小鼠胸膜炎的实验模型和体外研究人类外周单核细胞和鼠腹膜巨噬细胞，证实了 ML 诱导 LD 形成的能力。此外，感染细胞通过产生旁分泌信号将 LD 诱导传递给未感染的邻近细胞，其中 TLR2 和 TLR6 被证明是必需的。然而，TLR2 和 TLR6 的缺失仅部分影响带菌细胞中的 LD 形成，这表明除了 TLR2/6 之外，巨噬细胞对 ML 的识别还涉及先天免疫反应的替代受体。最后，观察到 LD 形成与 PGE（2）产生之间存在直接相关性，表明 ML 诱导的 LD 构成了类二十烷酸合成的细胞内部位，泡沫细胞可能是麻风病中颠覆免疫反应的关键调节因子。
