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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

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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.


MALDI-TOF mass spectra of liver tissues reveal high concentration of arachidonic acid (AA) in naturally S. mansoni-infected N. squamipes.(A, B) Mass spectra, from 301 to 307 m/z range showing peaks attributed to sodium adduct of the linoleic acid [M + Na]+ (m/z 303.03), AA (m/z 304.24) and sodium adduct of the oleic acid [M + Na]+ (m/z 305.26). (C, D) Mass spectra from 324 to 330 m/z range. The peak observed at 327 m/z represents sodium adduct of the AA [M + Na]+. Liver sections from uninfected and naturally S. mansoni-infected N. squamipes (n = 3 sections from each group) were cut on a cryostat (50 μm thickness) and analyzed without any labeling.
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pone.0166979.g006: MALDI-TOF mass spectra of liver tissues reveal high concentration of arachidonic acid (AA) in naturally S. mansoni-infected N. squamipes.(A, B) Mass spectra, from 301 to 307 m/z range showing peaks attributed to sodium adduct of the linoleic acid [M + Na]+ (m/z 303.03), AA (m/z 304.24) and sodium adduct of the oleic acid [M + Na]+ (m/z 305.26). (C, D) Mass spectra from 324 to 330 m/z range. The peak observed at 327 m/z represents sodium adduct of the AA [M + Na]+. Liver sections from uninfected and naturally S. mansoni-infected N. squamipes (n = 3 sections from each group) were cut on a cryostat (50 μm thickness) and analyzed without any labeling.

Mentions: In Fig 6A and 6B, the liver tissue mass spectra of lipid species are presented for N. squamipes samples for a mass range from m/z 302 to 307, which correspond mostly to PUFAs. In both uninfected and infected liver samples, the following PUFAs were identified within this range: AA (20:4) and linoleic acid (LA) (18:2), both omega-6. Moreover, oleic acid (OA) (18:1), which is a monounsaturated fatty acid, was also detected. The peak m/z 304.24 attributed to the ion [M]+ (C20H32O2) refers to AA. The other peaks are attributed to the presence of protonated molecules [M + H]+ and/or sodium adduct [M + Na]+, the most often chemical events observed during MALDI-TOF-MS analyses in the positive ion mode [35–37]. Thus, the peak m/z 303.23 can be attributed to the ion C18H32NaO2 [M + Na]+ and refers to the sodium adduct of the omega-6 LA while the peak m/z 305.25 refers to the [M + Na]+ of the OA (C18H34NaO2) [37]. We also observed sodium adduct to the AA [M + Na]+ (C20H32NaO2), revealed by a of peak m/z 327.23 (Fig 6C and 6D).


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
MALDI-TOF mass spectra of liver tissues reveal high concentration of arachidonic acid (AA) in naturally S. mansoni-infected N. squamipes.(A, B) Mass spectra, from 301 to 307 m/z range showing peaks attributed to sodium adduct of the linoleic acid [M + Na]+ (m/z 303.03), AA (m/z 304.24) and sodium adduct of the oleic acid [M + Na]+ (m/z 305.26). (C, D) Mass spectra from 324 to 330 m/z range. The peak observed at 327 m/z represents sodium adduct of the AA [M + Na]+. Liver sections from uninfected and naturally S. mansoni-infected N. squamipes (n = 3 sections from each group) were cut on a cryostat (50 μm thickness) and analyzed without any labeling.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5120838&req=5

pone.0166979.g006: MALDI-TOF mass spectra of liver tissues reveal high concentration of arachidonic acid (AA) in naturally S. mansoni-infected N. squamipes.(A, B) Mass spectra, from 301 to 307 m/z range showing peaks attributed to sodium adduct of the linoleic acid [M + Na]+ (m/z 303.03), AA (m/z 304.24) and sodium adduct of the oleic acid [M + Na]+ (m/z 305.26). (C, D) Mass spectra from 324 to 330 m/z range. The peak observed at 327 m/z represents sodium adduct of the AA [M + Na]+. Liver sections from uninfected and naturally S. mansoni-infected N. squamipes (n = 3 sections from each group) were cut on a cryostat (50 μm thickness) and analyzed without any labeling.
Mentions: In Fig 6A and 6B, the liver tissue mass spectra of lipid species are presented for N. squamipes samples for a mass range from m/z 302 to 307, which correspond mostly to PUFAs. In both uninfected and infected liver samples, the following PUFAs were identified within this range: AA (20:4) and linoleic acid (LA) (18:2), both omega-6. Moreover, oleic acid (OA) (18:1), which is a monounsaturated fatty acid, was also detected. The peak m/z 304.24 attributed to the ion [M]+ (C20H32O2) refers to AA. The other peaks are attributed to the presence of protonated molecules [M + H]+ and/or sodium adduct [M + Na]+, the most often chemical events observed during MALDI-TOF-MS analyses in the positive ion mode [35–37]. Thus, the peak m/z 303.23 can be attributed to the ion C18H32NaO2 [M + Na]+ and refers to the sodium adduct of the omega-6 LA while the peak m/z 305.25 refers to the [M + Na]+ of the OA (C18H34NaO2) [37]. We also observed sodium adduct to the AA [M + Na]+ (C20H32NaO2), revealed by a of peak m/z 327.23 (Fig 6C and 6D).

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.