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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.


Ultrastructure of LDs formed in the liver of uninfected and naturally S. mansoni-infected N. squamipes.(A-C) Electron micrographs of the hepatic tissue reveal electron lucent LDs with varied sizes within hepatocytes in both control (A) and infected (B, C) livers. Note in (B), a giant LD (arrow) in the hepatocyte cytoplasm. (D) TEM quantitative analyses show a high number of LDs per tissue area (P < 0.002). The range of LD diameter is shown in (E). Scale bar, 9 μm (A-C). Liver fragments were fixed in a mixture of paraformaldehyde/glutaraldehyde and processed for TEM. Quantitative analyses were performed in a total of 34,000 μm2 of hepatic tissue (17,000 μm2 from uninfected and 17,000 μm2 from infected animals) using the software ImageJ. Data represent mean ± S.E.M. ***P < 0.0001 for infected versus uninfected group.
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pone.0166979.g003: Ultrastructure of LDs formed in the liver of uninfected and naturally S. mansoni-infected N. squamipes.(A-C) Electron micrographs of the hepatic tissue reveal electron lucent LDs with varied sizes within hepatocytes in both control (A) and infected (B, C) livers. Note in (B), a giant LD (arrow) in the hepatocyte cytoplasm. (D) TEM quantitative analyses show a high number of LDs per tissue area (P < 0.002). The range of LD diameter is shown in (E). Scale bar, 9 μm (A-C). Liver fragments were fixed in a mixture of paraformaldehyde/glutaraldehyde and processed for TEM. Quantitative analyses were performed in a total of 34,000 μm2 of hepatic tissue (17,000 μm2 from uninfected and 17,000 μm2 from infected animals) using the software ImageJ. Data represent mean ± S.E.M. ***P < 0.0001 for infected versus uninfected group.

Mentions: In both non-infected and infected groups, hepatocytes exhibit LDs as distinct, non-membrane bound cytoplasmic sites mostly seen as electron-lucent organelles (Fig 3A–3C). Quantitative EM analyses using the software Image J confirmed a significant increase of LD numbers per tissue area in infected liver compared to the uninfected group (1.78 ± 0.19 in the control versus 3.20 ± 0.30 in infected group, mean ± SEM, P< 0.0002) (Fig 3D). Moreover, TEM clearly revealed that LDs greatly varied in size, with diameters ranging from less than 1 to 12 μm (Fig 3A–3C and 3E).


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
Ultrastructure of LDs formed in the liver of uninfected and naturally S. mansoni-infected N. squamipes.(A-C) Electron micrographs of the hepatic tissue reveal electron lucent LDs with varied sizes within hepatocytes in both control (A) and infected (B, C) livers. Note in (B), a giant LD (arrow) in the hepatocyte cytoplasm. (D) TEM quantitative analyses show a high number of LDs per tissue area (P < 0.002). The range of LD diameter is shown in (E). Scale bar, 9 μm (A-C). Liver fragments were fixed in a mixture of paraformaldehyde/glutaraldehyde and processed for TEM. Quantitative analyses were performed in a total of 34,000 μm2 of hepatic tissue (17,000 μm2 from uninfected and 17,000 μm2 from infected animals) using the software ImageJ. Data represent mean ± S.E.M. ***P < 0.0001 for infected versus uninfected group.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0166979.g003: Ultrastructure of LDs formed in the liver of uninfected and naturally S. mansoni-infected N. squamipes.(A-C) Electron micrographs of the hepatic tissue reveal electron lucent LDs with varied sizes within hepatocytes in both control (A) and infected (B, C) livers. Note in (B), a giant LD (arrow) in the hepatocyte cytoplasm. (D) TEM quantitative analyses show a high number of LDs per tissue area (P < 0.002). The range of LD diameter is shown in (E). Scale bar, 9 μm (A-C). Liver fragments were fixed in a mixture of paraformaldehyde/glutaraldehyde and processed for TEM. Quantitative analyses were performed in a total of 34,000 μm2 of hepatic tissue (17,000 μm2 from uninfected and 17,000 μm2 from infected animals) using the software ImageJ. Data represent mean ± S.E.M. ***P < 0.0001 for infected versus uninfected group.
Mentions: In both non-infected and infected groups, hepatocytes exhibit LDs as distinct, non-membrane bound cytoplasmic sites mostly seen as electron-lucent organelles (Fig 3A–3C). Quantitative EM analyses using the software Image J confirmed a significant increase of LD numbers per tissue area in infected liver compared to the uninfected group (1.78 ± 0.19 in the control versus 3.20 ± 0.30 in infected group, mean ± SEM, P< 0.0002) (Fig 3D). Moreover, TEM clearly revealed that LDs greatly varied in size, with diameters ranging from less than 1 to 12 μm (Fig 3A–3C and 3E).

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.