Schistosome infections induce significant changes in the host biliary proteome

Torre-Escudero, Eduardo de la; Pérez–Sánchez, Ricardo; Manzano-Román, Raúl; Oleaga, Ana

doi:10.1016/j.jprot.2014.11.009

Cited by 7 publications

(2 citation statements)

References 39 publications

(45 reference statements)

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“…While nonprotein bile components are well characterized, only a limited number of bile proteins have been identified due to technical challenges (29). Proteomic analysis has identified several proteins in bile (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). Notably, CPS1 has not been reported previously as a human bile component, although another urea cycle enzyme, ornithine transcarbamylase, was reported nearly 60 y ago as a bile component, and was studied as a potential marker of liver disease (41)(42)(43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

Constitutive release of CPS1 in bile and its role as a protective cytokine during acute liver injury

Park

DʼAlecy

Anderson

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Carbamoyl phosphate synthetase-1 (CPS1) is the major mitochondrial urea cycle enzyme in hepatocytes. It is released into mouse and human blood during acute liver injury, where is has a short half-life. The function of CPS1 in blood and the reason for its short half-life in serum are unknown. We show that CPS1 is released normally into mouse and human bile, and pathologically into blood during acute liver injury. Other cytoplasmic and mitochondrial urea cycle enzymes are also found in normal mouse bile. Serum, bile, and purified CPS1 manifest sedimentation properties that overlap with extracellular vesicles, due to the propensity of CPS1 to aggregate despite being released primarily as a soluble protein. During liver injury, CPS1 in blood is rapidly sequestered by monocytes, leading to monocyte M2-polarization and homing to the liver independent of its enzyme activity. Recombinant CPS1 (rCPS1), but not control r-transferrin, increases hepatic macrophage numbers and phagocytic activity. Notably, rCPS1 does not activate hepatic macrophages directly; rather, it activates bone marrow and circulating monocytes that then home to the liver. rCPS1 administration prevents mouse liver damage induced by Fas ligand or acetaminophen, but this protection is absent in macrophage-deficient mice. Moreover, rCPS1 protects from acetaminophen-induced liver injury even when given therapeutically after injury induction. In summary, CPS1 is normally found in bile but is released by hepatocytes into blood upon liver damage. We demonstrate a nonenzymatic function of CPS1 as an antiinflammatory protective cytokine during acute liver injury.

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Section: Discussionmentioning

confidence: 99%

Constitutive release of CPS1 in bile and its role as a protective cytokine during acute liver injury

Park

DʼAlecy

Anderson

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…As the gut and tegument represent key host–parasite interfaces and are the major sites of EV release by adult F. hepatica [ 16 , 18 , 19 , 20 ], these tissues were isolated by LMD and analysed by mass spectrometry ( Figure S1 ). A total of 226 gastrodermal cell proteins were identified (>2 matched peptides in at least two out of four replicates) ( Table 1 and Table S1A ).…”

Section: Resultsmentioning

confidence: 99%

Fasciola hepatica Gastrodermal Cells Selectively Release Extracellular Vesicles via a Novel Atypical Secretory Mechanism

Bennett

Torre-Escudero

Dermott

et al. 2022

IJMS

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The liver fluke, Fasciola hepatica, is an obligate blood-feeder, and the gastrodermal cells of the parasite form the interface with the host’s blood. Despite their importance in the host–parasite interaction, in-depth proteomic analysis of the gastrodermal cells is lacking. Here, we used laser microdissection of F. hepatica tissue sections to generate unique and biologically exclusive tissue fractions of the gastrodermal cells and tegument for analysis by mass spectrometry. A total of 226 gastrodermal cell proteins were identified, with proteases that degrade haemoglobin being the most abundant. Other detected proteins included those such as proton pumps and anticoagulants which maintain a microenvironment that facilitates digestion. By comparing the gastrodermal cell proteome and the 102 proteins identified in the laser microdissected tegument with previously published tegument proteomic datasets, we showed that one-quarter of proteins (removed by freeze–thaw extraction) or one-third of proteins (removed by detergent extraction) previously identified as tegumental were instead derived from the gastrodermal cells. Comparative analysis of the laser microdissected gastrodermal cells, tegument, and F. hepatica secretome revealed that the gastrodermal cells are the principal source of secreted proteins, as well as showed that both the gastrodermal cells and the tegument are likely to release subpopulations of extracellular vesicles (EVs). Microscopical examination of the gut caeca from flukes fixed immediately after their removal from the host bile ducts showed that selected gastrodermal cells underwent a progressive thinning of the apical plasma membrane which ruptured to release secretory vesicles en masse into the gut lumen. Our findings suggest that gut-derived EVs are released via a novel atypical secretory route and highlight the importance of the gastrodermal cells in nutrient acquisition and possible immunomodulation by the parasite.

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Ultrasonography of gallbladder abnormalities due to schistosomiasis

et al. 2016

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After malaria, schistosomiasis remains the most important tropical parasitic disease in large parts of the world. Schistosomiasis has recently re-emerged in Southern Europe. Intestinal schistosomiasis is caused by most Schistosoma (S.) spp. pathogenic to humans and leads to chronic inflammation and fibrosis of the colon as well as to liver fibrosis. Gallbladder abnormalities usually occur in patients with advanced hepatic portal fibrosis due to Schistosoma mansoni infection. Occasionally, gallbladder abnormalities have been seen also in children and occurring without associated overt liver abnormalities.The specific S. mansoni-induced gallbladder abnormalities detectable by ultrasound include typical hyperechogenic wall thickening with external gallbladder wall protuberances. The luminal wall surface is smooth. The condition is usually clinically silent although some cases of symptomatic cholecystitis have been described. The ultrasonographic Murphy response is negative. Gallbladder contractility is impaired but sludge and calculi occur rarely. Contrary to other trematodes such as liver flukes, S. mansoni does not obstruct the biliary tract. Advanced gallbladder fibrosis is unlikely to reverse after therapy.

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Schistosome infections induce significant changes in the host biliary proteome

Cited by 7 publications

References 39 publications

Constitutive release of CPS1 in bile and its role as a protective cytokine during acute liver injury

Constitutive release of CPS1 in bile and its role as a protective cytokine during acute liver injury

Fasciola hepatica Gastrodermal Cells Selectively Release Extracellular Vesicles via a Novel Atypical Secretory Mechanism

Ultrasonography of gallbladder abnormalities due to schistosomiasis

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