Profiling the serum proteome during Schistosoma mansoni infection in the BALB/c mice: A focus on the altered lipid metabolism as a key modulator of host-parasite interactions

Abstract

Schistosomiasis represents a condition in which every aspect of the disease, starting from skin invasion of the cercariae to egg laying by adult worms, incites a tissue response from the vertebrate host. This response, whether acute or chronic, leads to the appearance of reporter molecules of tissue injury in bodily fluids that could be surveyed as markers for disease diagnosis, status and prognosis. In this scenario, the serum proteome associated with a schistosome infection remains poorly explored; particularly by the use of high-throughput mass spectrometric instrumentation. In this study, we aimed to comparatively examine the serum proteome of control versus infected BALB/c mice, spanning the interval between the onset of egg laying and the peak of the acute phase of infection. Compositional analysis of the sera, using one dimensional reversed-phase fractionation of tryptic peptides coupled to mass spectrometry, allowed identification of 453 constituents. Among these, over 30% (143 molecules) were differentially present comparing sera from infected and non-infected mice, as revealed by quantitative label-free shotgun approach. The majority of proteins exhibiting altered levels was categorised as belonging to immune response (acute phase-related proteins) followed by those linked to lipid transport and metabolism. Inspection of the lipid profile from control and infected individuals demonstrated more pronounced and significant alterations in triglycerides, VLDL and HDL fractions (p<0,001), attesting for a disturbance in circulating lipid molecules, and suggesting a key role in host-parasite interactions. Our findings provide a global view of the serum proteome in the context of experimental schistosomiasis during the acute phase of infection. It contributes by listing key molecules that could be monitored to inform on the associated inflammatory disease status. We hope it will shed light into uncovered aspects of the Schistosoma mansoni parasitism in the vertebrate host, particularly those related to modulation of the lipid metabolism mediating immune responses.

High level of C3 is associated with Th2 immune response and liver fibrosis in patients with schistosomiasis

“…Previous studies showed that schistosoma infection could affect serum proteome, and that schistosoma could absorb complement and rapidly degrade selected complement proteins. 18 In recent years, clinical studies on schistosomiasis 6,19 indicated that the serum liver function indexes were affected by schistosomiasis infection.…”

“…The level of complement C4 was increased, while complement C3, a major component of globulin, 17 showed no significant difference but was in an obvious skewed distribution. Previous studies showed that schistosoma infection could affect serum proteome, and that schistosoma could absorb complement and rapidly degrade selected complement proteins 18 . In recent years, clinical studies on schistosomiasis 6,19 indicated that the serum liver function indexes were affected by schistosomiasis infection.…”

Progresses and challenges in Strongyloides spp. proteomics

“…Such analysis could however be particularly useful in revealing novel facets of the pathological mechanisms associated with human strongyloidiasis, especially when applied in comparative studies. Indeed, this strategy has already been successfully applied to the study of other helminthiases, including schistosomiasis, fasciolosis and echinococcosis, to identify proteins or biological processes altered in the pathological state compared to uninfected controls, during the disease progression or in response to treatment [66][67][68][69][70][71][72][73][74][75][76]. The most commonly investigated samples are plasma/serum and plasma/serumderived EVs (either from animal models or from patients), even though also tissue proteomics has been described [69,70].…”