A Microtus fortisprotein, serum albumin, is a novel inhibitor of Schistosoma japonicumschistosomula

Abstract

Schistosomiasis is an endemic parasite disease and praziquantel is the only drug currently in use to control this disease. Experimental and epidemiological evidence strongly suggests that Microtus fortis ( Mf ) is a naturally resistant vertebrate host of Schistosoma japonicum . In the present study, we found that Mf serum albumin ( Mf -albumin) and the conditioned medium of pcDNA3.1- Mf -albumin caused 46.2% and 38.7% schistosomula death rates in 96 h, respectively, which were significantly higher than that of the negative control (p < 0.05). We also found that mice injected with Mf -albumin had a 43.5% reduction in worm burden and a 48.1% reduction in liver eggs per gram (p < 0.05) in comparison to the control animals. To characterise the mechanisms involved in clearance, schistosomula were incubated with fluorescein isothiocyanate-labelled Mf -albumin and fluorescent enrichment effects were found in the gut lumen of schistosomula after 48 h of incubation. Next, digestive tract excretions from schistosomula were collected and the sensitivity of Mf -albumin to digestive tract excretions was evaluated. The results indicated that schistosomula digestive tract excretions showed indigestibility of Mf -albumin. The death of schistosomula could be partially attributed to the lack of digestion of Mf -albumin by digestive tract excretions during the development of the schistosomula stage. Therefore, these data indicate the potential of Mf -albumin as one of the major selective forces for schistosomiasis.

Genome assembly and transcriptome analysis provide insights into the anti-schistosome mechanism ofMicrotus fortis

“…A total of 33 innate immune genes were positively selected, which indicates the rapid evolution of immune system in M. Table 13). For the previously reported genes (ALB [17], HSP90α [15], KPNA2 [16]) that were possibly associated with M. fortis intrinsic resistance, we did not find any significant sites under positive selection.…”

A Panel of Stably Expressed Reference Genes for Real-Time qPCR Gene Expression Studies of Mallards (Anas platyrhynchos)

“…The fact that ALB tended to have higher expression in infected than uninfected individuals in lung, GI2 and GI4 tissues ( Fig 1 ) suggests that ALB may be upregulated in response to AIV infection in ducks. While albumin has not previously been shown to be associated with antiviral immune responses, it has been implicated in regulation of bacteria [ 69 ], yeast [ 69 , 70 ] and eukaryotic parasites [ 71 ]. The remaining genes displayed adequate stability in at least a subset of analyses, and we recommend that, at a minimum, these nine genes are included in future panels when testing stability of putative RGs in mallards.…”

Mechanisms of Resistance to Schistosoma japonicum Infection in Microtus fortis, the Natural Non-permissive Host

“…Moreover, albumin may play an important role in innate immunity (Gleeson and Dickson, 2015;Wilde and Katsounas, 2019). When schistosomula were cultured with purified albumin from the serum of M. fortis or a pcDNA3.1 plasmid encoding M. fortis albumin for 96 h in vitro, Li et al (2013) found that the reduction rates of the schistosomula were 46.2 and 38.7%, respectively, which were significantly higher than the rate of the negative control group. Furthermore, when purified albumin from M. fortis was injected into infected mice, the worm burden was reduced by 43.5%, and the eggs per gram in the liver was decreased by 48.1% at 6 weeks postinfection in comparison to the corresponding parameters in control animals (Li et al, 2013).…”

“…These results demonstrate that albumin in the serum may be an important factor involved in resistance in M. fortis. Interestingly, Li et al (2013) reported that M. fortis albumin was poorly digested by the digestive system of S. japonicum. Thus, it seems that the inability of S. japonicum to survive in M. fortis is attributed to the difficulty of digesting albumin for S. japonicum during development (Li et al, 2013).…”

“…Interestingly, Li et al (2013) reported that M. fortis albumin was poorly digested by the digestive system of S. japonicum. Thus, it seems that the inability of S. japonicum to survive in M. fortis is attributed to the difficulty of digesting albumin for S. japonicum during development (Li et al, 2013). Why can mouse albumin be digested by S. japonicum, while M. fortis albumin cannot?…”