The Sweeping Role of Cholesterol Depletion in the Persistence of Helicobacter pylori Infections

Morey, Pau; Meyer, Thomas F.

doi:10.1007/978-3-030-15138-6_9

Cited by 8 publications

(6 citation statements)

References 103 publications

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“…αCgT is produced by H. pylori in an inactive form which becomes activated after binding to the host cell membrane [299]. The absence of the αCgT gene is associated with significant dysregulations of the cholesterol uptake by the bacterium [300]. Glucosylation promoted by αCgT prevents H. pylori from the phagocytosis and immune responses induced by bacterial infection [301].…”

Section: Cholesteryl α-Glucosyltransferasementioning

confidence: 99%

Helicobacter pylori Virulence Factors—Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment

Baj

Forma

Sitarz

et al. 2020

Cells

205

163

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Gastric cancer constitutes one of the most prevalent malignancies in both sexes; it is currently the fourth major cause of cancer-related deaths worldwide. The pathogenesis of gastric cancer is associated with the interaction between genetic and environmental factors, among which infection by Helicobacter pylori (H. pylori) is of major importance. The invasion, survival, colonization, and stimulation of further inflammation within the gastric mucosa are possible due to several evasive mechanisms induced by the virulence factors that are expressed by the bacterium. The knowledge concerning the mechanisms of H. pylori pathogenicity is crucial to ameliorate eradication strategies preventing the possible induction of carcinogenesis. This review highlights the current state of knowledge and the most recent findings regarding H. pylori virulence factors and their relationship with gastric premalignant lesions and further carcinogenesis.

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Section: Cholesteryl α-Glucosyltransferasementioning

confidence: 99%

Helicobacter pylori Virulence Factors—Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment

Baj

Forma

Sitarz

et al. 2020

Cells

205

163

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“…The role of cholesterol metabolic reprogramming in persistent Listeria infection of epithelial cells deserves further investigation, given the role of cholesterol in the establishment of vacuolar niches for intracellular pathogens ( Samanta et al., 2017 ) and of oxysterols in host immune functions ( Cyster et al., 2014 ; Abrams et al., 2020 ). In addition, controlling cholesterol metabolism plays a key role in Mtb and Helicobacter pylori persistent infections ( Pandey and Sassetti, 2008 ; Morey and Meyer, 2019 ). In PMH, long-term Listeria infection was not associated with the cholesterol biosynthesis pathway.…”

Section: Discussionmentioning

confidence: 99%

An Immunomodulatory Transcriptional Signature Associated With Persistent Listeria Infection in Hepatocytes

Descoeudres¹,

Jouneau²,

Henry³

et al. 2021

Front. Cell. Infect. Microbiol.

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Listeria monocytogenes causes severe foodborne illness in pregnant women and immunocompromised individuals. After the intestinal phase of infection, the liver plays a central role in the clearance of this pathogen through its important functions in immunity. However, recent evidence suggests that during long-term infection of hepatocytes, a subpopulation of Listeria may escape eradication by entering a persistence phase in intracellular vacuoles. Here, we examine whether this long-term infection alters hepatocyte defense pathways, which may be instrumental for bacterial persistence. We first optimized cell models of persistent infection in human hepatocyte cell lines HepG2 and Huh7 and primary mouse hepatocytes (PMH). In these cells, Listeria efficiently entered the persistence phase after three days of infection, while inducing a potent interferon response, of type I in PMH and type III in HepG2, while Huh7 remained unresponsive. RNA-sequencing analysis identified a common signature of long-term Listeria infection characterized by the overexpression of a set of genes involved in antiviral immunity and the under-expression of many acute phase protein (APP) genes, particularly involved in the complement and coagulation systems. Infection also altered the expression of cholesterol metabolism-associated genes in HepG2 and Huh7 cells. The decrease in APP transcripts was correlated with lower protein abundance in the secretome of infected cells, as shown by proteomics, and also occurred in the presence of APP inducers (IL-6 or IL-1β). Collectively, these results reveal that long-term infection with Listeria profoundly deregulates the innate immune functions of hepatocytes, which could generate an environment favorable to the establishment of persistent infection.

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“…When H. pylori or related H. hepaticus of cholesterol α-glucosyl transferase-deficient mutant or wild-type strains were orogastrically inoculated to mice, the microbes of the mutant strains were more effectively cleared from the digestive organs of the recipients than those of the wild type [129,130]. Morey and Meyer [131] recently reported that depletion of cholesterol in the epithelial cells in host gastric glands by H. pylori infection destroys raft structure of their plasma membrane and prevents the signaling of IFN-γ and other pro-inflammatory cytokines thereby promoting the persistence of the infection. They also demonstrated that the escape from host immune surveillance is dependent on the activity of cholesterol α-glucosyltransferase in the pathogens although the roles of the resultant cholesteryl α-glucosides in the escape were not directly described [131].…”

Section: Gaucher Disease (Gd) and Parkinson's Disease (Pd)mentioning

confidence: 99%

“…Morey and Meyer [131] recently reported that depletion of cholesterol in the epithelial cells in host gastric glands by H. pylori infection destroys raft structure of their plasma membrane and prevents the signaling of IFN-γ and other pro-inflammatory cytokines thereby promoting the persistence of the infection. They also demonstrated that the escape from host immune surveillance is dependent on the activity of cholesterol α-glucosyltransferase in the pathogens although the roles of the resultant cholesteryl α-glucosides in the escape were not directly described [131].…”

Section: Gaucher Disease (Gd) and Parkinson's Disease (Pd)mentioning

confidence: 99%

Structure, metabolism and biological functions of steryl glycosides in mammals

Shimamura

2020

Biochemical Journal

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Steryl glycosides (SGs) are sterols glycosylated at their 3β-hydroxy group. They are widely distributed in plants, algae, and fungi, but are relatively rare in bacteria and animals. Glycosylation of sterols, resulting in important components of the cell membrane SGs, alters their biophysical properties and confers resistance against stress by freezing or heat shock to cells. Besides, many biological functions in animals have been suggested from the observations of SG administration. Recently, cholesteryl glucosides synthesized via the transglycosidation by glucocerebrosidases (GBAs) were found in the central nervous system of animals. Identification of patients with congenital mutations in GBA genes or availability of respective animal models will enable investigation of the function of such endogenously synthesized cholesteryl glycosides by genetic approaches. In addition, mechanisms of the host immune responses against pathogenic bacterial SGs have partially been resolved. This review is focused on the biological functions of SGs in mammals taking into consideration their therapeutic applications in the future.

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The Sweeping Role of Cholesterol Depletion in the Persistence of Helicobacter pylori Infections

Cited by 8 publications

References 103 publications

Helicobacter pylori Virulence Factors—Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment

Helicobacter pylori Virulence Factors—Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment

An Immunomodulatory Transcriptional Signature Associated With Persistent Listeria Infection in Hepatocytes

Structure, metabolism and biological functions of steryl glycosides in mammals

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