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

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.

Histological assessment of granulomas in natural and experimental Schistosoma mansoni infections using whole slide imaging

“…Both naturally and experimentally infected animals and their respective uninfected controls were anesthetized and euthanized as before [ 19 ], and organ fragments were collected and processed for histopathological studies as below. Animals were euthanized by exsanguination (full bleed) under deep anesthesia by cardiac puncture.…”

Alterations in the lipid profiles and circulating liver enzymes in individuals infected by Schistosoma mansoni

“…Nonetheless, a wide range of liver damage has been described in both human and animal infections. These include impaired protein synthesis 4 , reduced lipoprotein concentrations [5][6][7][8] , decreased erythrocyte counts and blood indexes, neutropenia, lymphopenia and eosinophilia 9 , increased circulating liver enzymes levels 10,11 , and hemostatic abnormalities 12,13 . Despite the variability in clinical signs, it remains unclear whether infected individuals without clinical complaints or symptoms present a detectable degree of liver dysfunction.…”

Molecular profiling of lipid droplets inside HuH7 Cells with Raman micro-spectroscopy

“…Raman imaging could locate and quantify the proportion of LDs in HuH7 cells under different feed conditions; such a quantification has relevance in the disease conditions. 41,42 Previous Raman imaging studies have also shown the capability of the technique to detect LDs in cells by mapping lipids. 43-47 However, molecular mapping of many different constituents of LD has never been demonstrated.…”