Accumulation of Cholesterol Esters in Macrophages Incubated With Mycobacteria in Vitro

Kondo, Eiko; Kanai, Koomi

doi:10.7883/yoken1952.29.123

Cited by 27 publications

(17 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is generally thought that the lipids in these cells are derived from mycobacterial lipids, including phospholipids and fatty acids (13). Similarly, foamy macrophages have previously been identified in advanced tuberculosis lesions (50,51). Our present data indicate that the lipids in Virchow's foamy macrophages represent, at least in part, the accumulation of host-derived oxidized phospholipids.…”

Section: Discussionsupporting

confidence: 84%

Host-derived oxidized phospholipids and HDL regulate innate immunity in human leprosy

Cruz¹,

Watson²,

Miller³

et al. 2008

J. Clin. Invest.

144

181

View full text Add to dashboard Cite

Intracellular pathogens survive by evading the host immune system and accessing host metabolic pathways to obtain nutrients for their growth. Mycobacterium leprae, the causative agent of leprosy, is thought to be the mycobacterium most dependent on host metabolic pathways, including host-derived lipids. Although fatty acids and phospholipids accumulate in the lesions of individuals with the lepromatous (also known as disseminated) form of human leprosy (L-lep), the origin and significance of these lipids remains unclear. Here we show that in human L-lep lesions, there was preferential expression of host lipid metabolism genes, including a group of phospholipases, and that these genes were virtually absent from the mycobacterial genome. Hostderived oxidized phospholipids were detected in macrophages within L-lep lesions, and 1 specific oxidized phospholipid, 1-palmitoyl-2-(5,6-epoxyisoprostane E 2 )-sn-glycero-3-phosphorylcholine (PEIPC), accumulated in macrophages infected with live mycobacteria. Mycobacterial infection and host-derived oxidized phospholipids both inhibited innate immune responses, and this inhibition was reversed by the addition of normal HDL, a scavenger of oxidized phospholipids, but not by HDL from patients with L-lep. The accumulation of host-derived oxidized phospholipids in L-lep lesions is strikingly similar to observations in atherosclerosis, which suggests that the link between host lipid metabolism and innate immunity contributes to the pathogenesis of both microbial infection and metabolic disease.

show abstract

Section: Discussionsupporting

confidence: 84%

Host-derived oxidized phospholipids and HDL regulate innate immunity in human leprosy

Cruz¹,

Watson²,

Miller³

et al. 2008

J. Clin. Invest.

144

181

View full text Add to dashboard Cite

show abstract

“…Fatty acids and cholesterol appeared in necrotic area. Similar findings described Hori et al (lg53a,b), Cerny (1965), Kondo and Kanai (1976). It was evident that caseous necrosis developed through steatosis of cells.…”

Section: Discussionsupporting

confidence: 87%

“…Later the presence of neutral fats in tuberculous process was studied by Hori et al (1953a, b), Cerny (1965) and the same authors have described in caseous necrosis the presence of fatty acids and cholesterol. These findings were confirmed by Kondo and Kanai (1976).…”

supporting

confidence: 59%

Histopathology and Histochemistry of Yersin Type Tuberculosis in Rabbits. Histochemical Study of Development of the Disease after Infection with Mycobacterium avium

Cerný¹

1979

Acta Vet. Brno

View full text Add to dashboard Cite

Cerny L.: Histopathology and Histochemistry of Yersin Type Tuberculosis in Rabbits. Histochemical Study of Development of the Disease after Infection with Mycobacterium avium. Acta vet. Brno, 48, 1979: 53-60. Organs of rabbits infected intravenously Mycobacterium avium were studied to reveal dynamics of changes in content of nucleic acids, carbohydrates and lipid substances and formation of fibres during development of Yersin type tuberculosis.Macrophages, young epitheloid cells and giant cells contained ribonucleic acid in their cytoplasm and nucleoli indicative of high activity of these cells. Gradually, amount of RNA in these cells diminished, first from their cytoplasm and then from the nucleoli and in prenecrotic stage the cells did not contain RNA at all.Along with the development of tuberculous process, in the cells of epitheloid and giant type content of PAS-positive carbohydrates increased. Greater part of these were glycogen while caseous material contained complexes of carbohydrates and proteins.In the cytoplasm of epitheloid and giant cells in the center of tuberculous foci, in necrotizing cells and in caseous material neutral fats, phospholipids, in later stages cholesterol and fatty acids were present. This finding showed that there was a metabolic disturbance of hypoxemic type.Formation of reticulin fibres in tuberculous lesions was connected with presence of acid mucopolysaccharides.

show abstract

“…Mycobacterium-dependent accumulation of cholesterol esters in macrophages has been observed (9), and recently M. tuberculosis genes were shown to encode cholesterolmodifying activities that contribute to virulence (2,19,21,22).…”

Section: Discussionmentioning

confidence: 99%

igr Genes and Mycobacterium tuberculosis Cholesterol Metabolism

et al. 2009

View full text Add to dashboard Cite

Recently, cholesterol was identified as a physiologically important nutrient for Mycobacterium tuberculosis survival in chronically infected mice. However, it remained unclear precisely when cholesterol is available to the bacterium and what additional bacterial functions are required for its metabolism. Here, we show that the igr locus, which we previously found to be essential for intracellular growth and virulence of M. tuberculosis, is required for cholesterol metabolism. While igr-deficient strains grow identically to the wild type in the presence of short-and long-chain fatty acids, the growth of these bacteria is completely inhibited in the presence of cholesterol. Interestingly, this mutant is still able to respire under cholesterol-dependent growth inhibition, suggesting that the bacteria can metabolize other carbon sources during cholesterol toxicity. Consistent with this hypothesis, we found that the growth-inhibitory effect of cholesterol in vitro depends on cholesterol import, as mutation of the mce4 sterol uptake system partially suppresses this effect. In addition, the ⌬igr mutant growth defect during the early phase of disease is completely suppressed by mutating mce4, implicating cholesterol intoxication as the primary mechanism of attenuation. We conclude that M. tuberculosis metabolizes cholesterol throughout infection.

show abstract

Accumulation of Cholesterol Esters in Macrophages Incubated With Mycobacteria in Vitro

Cited by 27 publications

References 8 publications

Host-derived oxidized phospholipids and HDL regulate innate immunity in human leprosy

Host-derived oxidized phospholipids and HDL regulate innate immunity in human leprosy

Histopathology and Histochemistry of Yersin Type Tuberculosis in Rabbits. Histochemical Study of Development of the Disease after Infection with Mycobacterium avium

igr Genes and Mycobacterium tuberculosis Cholesterol Metabolism

Contact Info

Product

Resources

About