Suppress signalling by extracellular signal-regulated kinase in haemocytes from S. mansoni-susceptible B. glabrata and that such suppression likely affects HSP70 and NO levels in a dose dependent fashion. Response to enable it to establish an infection. Strikingly, ESPs did not affect ERK signalling in haemocytes from a S. mansonirefractory B. glabrata strain demonstrating that haemocytes from a resistant strain reacted differently to the presence of parasite ESPs, indicating a different response at the molecular level, which may be responsible for the outcome of infection. Thus, by producing ESPs schistosomes seem able to modulate the defence responses of host snail haemocytes to facilitate parasite survival. However, the extent to which ESPs modulate global gene expression of haemocytes remains an important and unanswered question. Although cDNA microarrays and other techniques have been used to determine effects of S. mansoni on B. glabrata haemocyte gene expression profiles, including comparing between schistosome-resistant and -susceptible strains, this is the first study to explore specifically gene expression patterns in haemocytes of these snails when exposed to S. mansoni larval transformation products.
Defining haemocyte gene expression patterns in this way has permitted the interrogation of host differences when exposed to components released by the parasite during transformation, rather than those that might arise directly, or indirectly, in response to interactions between haemocytes and the schistosome surface. Ninety-eight genes were found differentially expressed representing 91 different proteins, with 57 genes being resistant-specific and 41 being susceptible-specific. Because haemocytes were exposed to ESPs for 1 h, we consider the differences to best represent those that might prevail during an immediate/early response in haemocytes, rather than those that would occur indirectly as a consequence of cellular feedback mechanisms. The 60 differentially expressed genes found here that correspond with those identified in our previous studies following infection of B. glabrata with S. mansoni signify those that are either: 1) differentially expressed in the resistant or susceptible snail haemocytes before exposure and are thus constitutive phenotypic differences between the snail strains ; or 2) expressed differentially or in vivo in response to ESPs released by the transforming schistosome larvae.
In agreement with our evidence, a recent publication showed that seven validated pancreatic cancer-specific mRNA markers and GAPDH have been detected in mouse salivary and bloodderived exosomes in a pancreatic cancer mouse model, and some of these mRNA markers were abolished when tumor cell exosome biogenesis was blocked. Another interesting study found that mice bearing melanoma tumors have overlapping transcriptomic signatures in two tissues: the tumor itself, and the salivary gland. Yet, it was concluded that salivary transcriptomic regulation was achieved through tumor cell-released mediators, such as growth factors and other inducers. However, whether the induction of salivary molecular signatures were disease specific biomolecules directly shuttled into saliva through ELMs, or the result of a synergistic interplay between salivary glands and tumor-derived mediators, including growth factor and ELMs, remain largely unknown.