Lasers and Time-Traveling Schistosomes in Space

I had the recent privilege of reading a very interesting paper in press by Chuah et al. in the Journal of Leukocyte Biology. The core technique of the publication is laser capture microdissection (LCM), which combines microscopy with the isolation and analysis of cells of interest:

Demonstration of liver granuloma section before (panel A) and after (panel G) laser capture microdissection of regions of interest.
Demonstration of liver granuloma section before (panel A) and after (panel G) laser capture microdissection of regions of interest.

The paper describes, for the first time, gene expression within various zones of liver granulomata induced by Schistosoma japonicum egg deposition. S. japonicum, one of two major parasitic worm species which cause human liver and intestinal schistosomiasis, is the cousin of Schistosoma haematobium, the etiologic agent of urogenital schistosomiasis.

Like all schistosome worms, S. japonicum worm eggs induce the formation of granulomata, dense collections of leukocytes, fibroblasts, and scar tissue. These features of schistosome egg-induced pathology were characterized many decades ago. However, a comprehensive analysis of the transcriptome in this setting, particularly with regards to how it relates temporally and spatially to different regions of egg granulomata, has until now never been undertaken.

Using LCM combined with microarrays, the authors demonstrated that different zones of liver granulomata tended to exhibit differential gene expression that segregated along specific functional pathways, including those involving neutrophils and fibrosis. Indeed, Chuah et al. bolster their LCM-derived neutrophil findings by demonstrating the presence of neutrophil extracellular traps (NETs) in S. japonicum but not Schistosoma mansoni liver granulomata. This confirms prior observations that S. japonicum liver granulomata tend to feature larger numbers of neutrophils than granulomata caused in the liver and bladder by S. mansoni and S. haematobium eggs, respectively. These findings point to tissue- and schistosome species-specific aspects of granuloma biology, an area of inquiry near and dear to our research group’s collective heart.

A better understanding of how various schistosomal granulomata form could reveal new therapeutic approaches for the unfortunate people who develop liver or kidney failure due to severe schistosomiasis. Although schistosomes currently can’t travel through time (or outer space – yet!), if they could, we’re certain that we could ask them why they exhibit tissue tropism. In the meantime, we’ll have to rely on tools like LCM with literal laser-like precision.