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New insights into the pathogenesis of leprosy: contribution of subversion of host cell metabolism to bacterial persistence, disease progression, and transmission.

Abstract

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.

More information

Type
Journal Article
Author
de Macedo C
Lara F
Pinheiro R
Schmitz V
de Berrêdo-Pinho M
Pereira G
Pessolani M
Year of Publication
2020
Journal
F1000Research
Volume
9
Date Published
01/2020
Language
eng
ISSN Number
2046-1402
DOI
10.12688/f1000research.21383.1
Alternate Journal
F1000Res
PMID
32051758
Publication Language
eng