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Natural Schistosoma mansoni Infection in the Wild Reservoir Nectomys squamipes Leads to Excessive Lipid Droplet Accumulation in Hepatocytes in the Absence of Liver Functional Impairment

View Article: PubMed Central - PubMed

ABSTRACT

Schistosomiasis is a neglected tropical disease of a significant public health impact. The water rat Nectomys squamipes is one of the most important non-human hosts in the schistosomiasis mansoni transmission in Brazil, being considered a wild reservoir. Cellular mechanisms that contribute to the physiological adaptation of this rodent to the Schistosoma mansoni parasite are poorly understood. Here we identified, for the first time, that a hepatic steatosis, a condition characterized by excessive lipid accumulation with formation of lipid droplets (LDs) within hepatocytes, occurs in response to the natural S. mansoni infection of N. squamipes, captured in an endemic region. Significant increases of LD area in the hepatic tissue and LD numbers/hepatocyte, detected by quantitative histopathological and ultrastructural analyses, were paralleled by increased serum profile (total cholesterol and triglycerides) in infected compared to uninfected animals. Raman spectroscopy showed high content of polyunsaturated fatty acids (PUFAs) in the liver of both groups. MALDI-TOFF mass spectroscopy revealed an amplified pool of omega-6 PUFA arachidonic acid in the liver of infected animals. Assessment of liver functional activity by the levels of hepatic transaminases (ALT and AST) did not detect any alteration during the natural infection. In summary, this work demonstrates that the natural infection of the wild reservoir N. squamipes with S. mansoni elicits hepatic steatosis in the absence of liver functional harm and that accumulation of lipids, markedly PUFAs, coexists with low occurrence of inflammatory granulomatous processes, suggesting that lipid stores may be acting as a protective mechanism for dealing with the infection.

No MeSH data available.


Raman spectra reveal high content of polyunsaturated fatty acids (PUFAs) in both uninfected and infected liver of N. squamipes.(A) The band at 3015 cm-1 is characteristic of PUFAs and is more prominent in arachidonic acid (AA) when compared to other PUFAs. The degree of unsaturation is shown in (B). Liver fragments of N. squamipes naturally infected and uninfected were fixed and analyzed by Raman spectroscopy without labeling. AA spectrum was obtained from pure AA (catalog number A3555, Sigma-Aldrich) diluted in ethanol. Data are representative of 3 independent experiments.
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pone.0166979.g005: Raman spectra reveal high content of polyunsaturated fatty acids (PUFAs) in both uninfected and infected liver of N. squamipes.(A) The band at 3015 cm-1 is characteristic of PUFAs and is more prominent in arachidonic acid (AA) when compared to other PUFAs. The degree of unsaturation is shown in (B). Liver fragments of N. squamipes naturally infected and uninfected were fixed and analyzed by Raman spectroscopy without labeling. AA spectrum was obtained from pure AA (catalog number A3555, Sigma-Aldrich) diluted in ethanol. Data are representative of 3 independent experiments.

Mentions: To explore the molecular properties of lipids within the liver of N. squamipes, we next used Raman spectroscopy. This technique provides information about the chemical composition of the biological sample, with the advantages of minimal sample preparation, without need of labeling and free from water interference due to the low cross-section of water for the Raman effect [30]. The result is showed by the Raman spectrum, where frequencies of characteristic Raman bands provide information of the composition of samples and the intensity of Raman bands is proportional to the relative concentration of a compound [30]. Fig 5A shows the mean Raman spectra (average of triplicates) found in the animals studied. The Raman spectra of hepatic tissues showed vibrational modes of lipids, compounds of interest in this study, but it has also been observed vibrational modes of other compounds, such as proteins and heme group. The saturated lipid characteristic bands are observed at 1301 and 1446 cm-1 and they are assigned to CH2 deformation vibrations. The bands in the region of 1659 cm-1, 1256 and 3015 cm-1 reveal the presence of unsaturation. Other Raman bands in the tissue spectra may be assigned to the presence of proteins and heme group [31].


Natural Schistosoma mansoni Infection in the Wild Reservoir Nectomys squamipes Leads to Excessive Lipid Droplet Accumulation in Hepatocytes in the Absence of Liver Functional Impairment
Raman spectra reveal high content of polyunsaturated fatty acids (PUFAs) in both uninfected and infected liver of N. squamipes.(A) The band at 3015 cm-1 is characteristic of PUFAs and is more prominent in arachidonic acid (AA) when compared to other PUFAs. The degree of unsaturation is shown in (B). Liver fragments of N. squamipes naturally infected and uninfected were fixed and analyzed by Raman spectroscopy without labeling. AA spectrum was obtained from pure AA (catalog number A3555, Sigma-Aldrich) diluted in ethanol. Data are representative of 3 independent experiments.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5120838&req=5

pone.0166979.g005: Raman spectra reveal high content of polyunsaturated fatty acids (PUFAs) in both uninfected and infected liver of N. squamipes.(A) The band at 3015 cm-1 is characteristic of PUFAs and is more prominent in arachidonic acid (AA) when compared to other PUFAs. The degree of unsaturation is shown in (B). Liver fragments of N. squamipes naturally infected and uninfected were fixed and analyzed by Raman spectroscopy without labeling. AA spectrum was obtained from pure AA (catalog number A3555, Sigma-Aldrich) diluted in ethanol. Data are representative of 3 independent experiments.
Mentions: To explore the molecular properties of lipids within the liver of N. squamipes, we next used Raman spectroscopy. This technique provides information about the chemical composition of the biological sample, with the advantages of minimal sample preparation, without need of labeling and free from water interference due to the low cross-section of water for the Raman effect [30]. The result is showed by the Raman spectrum, where frequencies of characteristic Raman bands provide information of the composition of samples and the intensity of Raman bands is proportional to the relative concentration of a compound [30]. Fig 5A shows the mean Raman spectra (average of triplicates) found in the animals studied. The Raman spectra of hepatic tissues showed vibrational modes of lipids, compounds of interest in this study, but it has also been observed vibrational modes of other compounds, such as proteins and heme group. The saturated lipid characteristic bands are observed at 1301 and 1446 cm-1 and they are assigned to CH2 deformation vibrations. The bands in the region of 1659 cm-1, 1256 and 3015 cm-1 reveal the presence of unsaturation. Other Raman bands in the tissue spectra may be assigned to the presence of proteins and heme group [31].

View Article: PubMed Central - PubMed

ABSTRACT

Schistosomiasis is a neglected tropical disease of a significant public health impact. The water rat Nectomys squamipes is one of the most important non-human hosts in the schistosomiasis mansoni transmission in Brazil, being considered a wild reservoir. Cellular mechanisms that contribute to the physiological adaptation of this rodent to the Schistosoma mansoni parasite are poorly understood. Here we identified, for the first time, that a hepatic steatosis, a condition characterized by excessive lipid accumulation with formation of lipid droplets (LDs) within hepatocytes, occurs in response to the natural S. mansoni infection of N. squamipes, captured in an endemic region. Significant increases of LD area in the hepatic tissue and LD numbers/hepatocyte, detected by quantitative histopathological and ultrastructural analyses, were paralleled by increased serum profile (total cholesterol and triglycerides) in infected compared to uninfected animals. Raman spectroscopy showed high content of polyunsaturated fatty acids (PUFAs) in the liver of both groups. MALDI-TOFF mass spectroscopy revealed an amplified pool of omega-6 PUFA arachidonic acid in the liver of infected animals. Assessment of liver functional activity by the levels of hepatic transaminases (ALT and AST) did not detect any alteration during the natural infection. In summary, this work demonstrates that the natural infection of the wild reservoir N. squamipes with S. mansoni elicits hepatic steatosis in the absence of liver functional harm and that accumulation of lipids, markedly PUFAs, coexists with low occurrence of inflammatory granulomatous processes, suggesting that lipid stores may be acting as a protective mechanism for dealing with the infection.

No MeSH data available.