02130nas a2200289   4500000000100000008004100001260001200042653001200054653002200066653002000088653001100108653001500119653001800134653002300152100001600175700001100191700001500202700001400217700002400231700001400255700001600269245016700285856004700452490000600499520132100505022001401826       2020                            d  c01/202010aleprosy10adisease tolerance10aimmune response10alipids10ametabolism10amycobacterium10aRegulatory T cells1 ade Macedo C1 aLara F1 aPinheiro R1 aSchmitz V1 ade Berrêdo-Pinho M1 aPereira G1 aPessolani M00aNew insights into the pathogenesis of leprosy: contribution of subversion of host cell metabolism to bacterial persistence, disease progression, and transmission.  uhttps://f1000research.com/articles/9-70/v10 v93 a<p>Chronic infection by the obligate intracellular pathogen  may lead to the development of leprosy. Of note, in the lepromatous clinical form of the disease, failure of the immune system to constrain infection allows the pathogen to reproduce to very high numbers with minimal clinical signs, favoring transmission. The bacillus can modulate cellular metabolism to support its survival, and these changes directly influence immune responses, leading to host tolerance, permanent disease, and dissemination. Among the metabolic changes, upregulation of cholesterol, phospholipids, and fatty acid biosynthesis is particularly important, as it leads to lipid accumulation in the host cells (macrophages and Schwann cells) in the form of lipid droplets, which are sites of polyunsaturated fatty acid-derived lipid mediator biosynthesis that modulate the inflammatory and immune responses. In Schwann cells, energy metabolism is also subverted to support a lipogenic environment. Furthermore, effects on tryptophan and iron metabolisms favor pathogen survival with moderate tissue damage. This review discusses the implications of metabolic changes on the course of  infection and host immune response and emphasizes the induction of regulatory T cells, which may play a pivotal role in immune modulation in leprosy.</p>  a2046-1402