Chronic whipworm infection exacerbates Schistosoma mansoni egg-induced hepatopathology in non-human primates

慢性鞭虫感染加剧非人类灵长类动物曼氏血吸虫卵引起的肝病理

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作者:Loc Le, Sabiha Khatoon, Paola Jiménez, Christopher Peterson, Rebecca Kernen, Weidong Zhang, Adebayo J Molehin, Samra Lazarus, Justin Sudduth, Jordan May, Souvik Karmakar, Juan U Rojo, Gul Ahmad, Workineh Torben, David Carey, Roman F Wolf, James F Papin, Afzal A Siddiqui

Background

Schistosomiasis continues to inflict significant morbidity and mortality in the tropical and subtropical regions of the world. The disease endemicity overlaps with the transmission of other parasitic diseases. Despite the ubiquity of polyparasitism in tropical regions, particularly in rural communities, little is known about the impact of multiple helminth infections on disease progression. In this pilot study, we describe the influence of chronic Trichuris trichiura infection on Schistosoma mansoni egg-induced hepatopathology in infected baboons.

Conclusions

Underlying chronic whipworm infection intensified schistosome egg-induced liver pathology in infected baboons. RNA-Seq analysis provided insight into pathways associated with increased liver damage, corroborating histological findings.

Methods

Baboons with or without underlying whipworm infection were challenged with S. mansoni cercariae to establish schistosomiasis. Adult S. mansoni worms were recovered by perfusion and enumerated, hepatic granulomas were quantified via light microscopy, and transcriptional profiling of tissues were completed using RNA sequencing technologies.

Results

Co-infection with both S. mansoni and T. trichiura resulted in higher female schistosome worm burden and significantly larger liver granuloma sizes. Systems biology analyses of peripheral blood mononuclear cells (PBMC) revealed pathways associated with increased liver damage in co-infected baboons. Conclusions: Underlying chronic whipworm infection intensified schistosome egg-induced liver pathology in infected baboons. RNA-Seq analysis provided insight into pathways associated with increased liver damage, corroborating histological findings.

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