2006
DOI: 10.1111/j.1462-5822.2005.00617.x
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Cholesterol depletion in Mycobacterium avium-infected macrophages overcomes the block in phagosome maturation and leads to the reversible sequestration of viable mycobacteria in phagolysosome-derived autophagic vacuoles

Abstract: SummaryPhagocytic entry of mycobacteria into macrophages requires the presence of cholesterol in the plasma membrane. This suggests that pathogenic mycobacteria may require cholesterol for their subsequent intra-cellular survival in non-maturing phagosomes. Here we report on the effect of cholesterol depletion on pre-existing phagosomes in mouse bone marrowderived macrophages infected with Mycobacterium avium . Cholesterol depletion with methyl-β β β β -cyclodextrin resulted in a loosening of the close apposit… Show more

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Cited by 99 publications
(103 citation statements)
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“…The intraphagosomal pH of all strains started to decline within minutes, and at 150 min after infection wild-type phagosomes were modestly acidified with a mean pH of 6.4, while phagosomes containing heat-inactivated wild-type bacteria were acidified to pH 5.8. These levels of intraphagosomal pH for live and dead mycobacteria are consistent with data reported elsewhere (de Chastellier & Thilo, 2006;Russell et al, 2005;Sturgill-Koszycki et al, 1994). The pH of the lspA : : aph phagosomes was 6.3, which is not significantly different from that of M. tuberculosis wild-type phago- Values represent the mean±SD (error bars) of four (resting BMDM) and three (activated BMDM) independent experiments.…”
Section: Acidification Of Lspa : : Aph Phagosomessupporting
confidence: 78%
“…The intraphagosomal pH of all strains started to decline within minutes, and at 150 min after infection wild-type phagosomes were modestly acidified with a mean pH of 6.4, while phagosomes containing heat-inactivated wild-type bacteria were acidified to pH 5.8. These levels of intraphagosomal pH for live and dead mycobacteria are consistent with data reported elsewhere (de Chastellier & Thilo, 2006;Russell et al, 2005;Sturgill-Koszycki et al, 1994). The pH of the lspA : : aph phagosomes was 6.3, which is not significantly different from that of M. tuberculosis wild-type phago- Values represent the mean±SD (error bars) of four (resting BMDM) and three (activated BMDM) independent experiments.…”
Section: Acidification Of Lspa : : Aph Phagosomessupporting
confidence: 78%
“…All these may be related with the fact that cholesterol is critical for intracellular survival of Mtb in the host cell (Pandey et al, 2008). Studies showing that cholesterol depletion of cells could overcome the pathogen induced phagosome maturation and autophagy block provided further support to the claims (Chastellier et al, 2006).In the present study it was claimed that both serum and dietary cholesterol have association with the development and outcome of active tuberculosis on humans. We were not able to predict the nature of the association as the literature provides no clear and consistent association.…”
Section: Resultssupporting
confidence: 62%
“…Cholesterol depletion was also shown to have an overcoming effect on the phagosome maturation block in M. avium infected macrophages (Chastellier et al, 2006). Foamy macrophages (FM) are lipid loaded macrophages generated from the massive uptake of LDL and its intra-cytoplasmic accumulation as cholesterol-esters.…”
Section: Issn: 2319-7706 Volume 6 Number 12 (2017) Pp 4056-4073mentioning
confidence: 99%
“…However, the induction of autophagy by cholesterol depletion of Mycobacterium aviuminfected macrophages failed to impact bacterial survival (26). Despite this disparity, we were able to reproduce bacterial killing in M. tuberculosis-infected BMM⌽ (SI Fig.…”
Section: Resultsmentioning
confidence: 64%