Pathogenic mycobacterium upregulates cholesterol 25-hydroxylase to promote granuloma development via foam cell formation

Zhou, Shuang; Zhang, Ding; Li, Dan; Wang, Hankun; Ding, Cairong; Song, Jingrui; Huang, Weifeng; Xia, Xuan; Zhou, Ziwei; Han, Shanshan; Jin, Zhu; Yan, Bo; Gonzales, Jacqueline; Via, Laura E.; Zhang, Lu; Wang, Decheng

doi:10.1016/j.isci.2024.109204

Cited by 3 publications

(2 citation statements)

References 58 publications

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“…The study by Korf et al demonstrated that the number of LLMs has increased in Mtb-infected LXRα −/− or LXRα −/− LXRβ −/− mice, suggesting that LXR could be a regulator of LLMs [ 56 ]. Another cholesterol mediator, cholesterol 25-hydroxylase (CH25H), was found to be upregulated during granuloma development [ 57 ]. A reduction in the number of LLMs was observed in the Raw 264.7 cells after CH25H silencing, followed by a decrease in adipocyte differentiation-related protein (ADRP) [ 57 ].…”

Section: Llms In Tbmentioning

confidence: 99%

“…Another cholesterol mediator, cholesterol 25-hydroxylase (CH25H), was found to be upregulated during granuloma development [ 57 ]. A reduction in the number of LLMs was observed in the Raw 264.7 cells after CH25H silencing, followed by a decrease in adipocyte differentiation-related protein (ADRP) [ 57 ]. Furthermore, Jaisinghani et al published one study showing that the knockdown of diacylglycerol acyltransferases-1 ( DGAT1 ) could inhibit LLM formation [ 58 ].…”

Section: Llms In Tbmentioning

confidence: 99%

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Lipid-Laden Macrophages in Pulmonary Diseases

Zhu,

Choi,

Somanath

et al. 2024

Cells

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Pulmonary surfactants play a crucial role in managing lung lipid metabolism, and dysregulation of this process is evident in various lung diseases. Alternations in lipid metabolism lead to pulmonary surfactant damage, resulting in hyperlipidemia in response to lung injury. Lung macrophages are responsible for recycling damaged lipid droplets to maintain lipid homeostasis. The inflammatory response triggered by external stimuli such as cigarette smoke, bleomycin, and bacteria can interfere with this process, resulting in the formation of lipid-laden macrophages (LLMs), also known as foamy macrophages. Recent studies have highlighted the potential significance of LLM formation in a range of pulmonary diseases. Furthermore, growing evidence suggests that LLMs are present in patients suffering from various pulmonary conditions. In this review, we summarize the essential metabolic and signaling pathways driving the LLM formation in chronic obstructive pulmonary disease, pulmonary fibrosis, tuberculosis, and acute lung injury.

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Section: Llms In Tbmentioning

confidence: 99%

Section: Llms In Tbmentioning

confidence: 99%

Lipid-Laden Macrophages in Pulmonary Diseases

Zhu,

Choi,

Somanath

et al. 2024

Cells

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IQGAP1 domesticates macrophages to favor mycobacteria survival via modulating NF-κB signal and augmenting VEGF secretion

Wen,

Li,

Wang

et al. 2024

International Immunopharmacology

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The role of cholesterol and its oxidation products in tuberculosis pathogenesis

Roth,

Philips,

Chandra

2024

Immunometabolism

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Mycobacterium tuberculosis causes tuberculosis (TB), one of the world’s most deadly infections. Lipids play an important role in M. tuberculosis pathogenesis. M. tuberculosis grows intracellularly within lipid-laden macrophages and extracellularly within the cholesterol-rich caseum of necrotic granulomas and pulmonary cavities. Evolved from soil saprophytes that are able to metabolize cholesterol from organic matter in the environment, M. tuberculosis inherited an extensive and highly conserved machinery to metabolize cholesterol. M. tuberculosis uses this machinery to degrade host cholesterol; the products of cholesterol degradation are incorporated into central carbon metabolism and used to generate cell envelope lipids, which play important roles in virulence. The host also modifies cholesterol by enzymatically oxidizing it to a variety of derivatives, collectively called oxysterols, which modulate cholesterol homeostasis and the immune response. Recently, we found that M. tuberculosis converts host cholesterol to an oxidized metabolite, cholestenone, that accumulates in the lungs of individuals with TB. M. tuberculosis encodes cholesterol-modifying enzymes, including a hydroxysteroid dehydrogenase, a putative cholesterol oxidase, and numerous cytochrome P450 monooxygenases. Here, we review what is known about cholesterol and its oxidation products in the pathogenesis of TB. We consider the possibility that the biological function of cholesterol metabolism by M. tuberculosis extends beyond a nutritional role.

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Pathogenic mycobacterium upregulates cholesterol 25-hydroxylase to promote granuloma development via foam cell formation

Cited by 3 publications

References 58 publications

Lipid-Laden Macrophages in Pulmonary Diseases

Lipid-Laden Macrophages in Pulmonary Diseases

IQGAP1 domesticates macrophages to favor mycobacteria survival via modulating NF-κB signal and augmenting VEGF secretion

The role of cholesterol and its oxidation products in tuberculosis pathogenesis

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