"Immune modulation by the salmon louse - time to shift targets"
A most remarkable feature of the Atlantic salmon louse is its ability to neutralize practically all immune responses by its host, the Atlantic salmon. Except for some very limited local reaction, the louse is barely visible to the immune system. What may be the result of millions of years of co-evolution and a molecular arms-race between parasite and host has resulted in some sort of armistice in favor of tolerating the parasite. How, and even if, the salmon louse actively gains the upper hand is not well understood. More and more evidence points into the direction that parasites can suppress, or “modulate”, the immune system of their host by excreted proteins or other compounds.
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Prostaglandins are lipid compounds that have functions akin to hormones and are found in most animals, including the salmon louse. When they were first discovered in 1935, it was believed that they were exclusively secreted by the human prostate, and hence the name. Prostaglandins are expressed in many different tissues and have different roles in e.g. vasodilation and inflammation.
For some time now, an idea about prostaglandin E2 (PGE2), a subtype of prostaglandins found in the salmon louse, has been discussed at sea lice meetings and conferences. It is believed that the salmon louse can produce PGE2 as it is released into sea water when stimulated with dopamine [1]. When salmon cells are treated with PGE2 it is recognized by a receptor and the cells respond in a certain way depending on the concentration of PGE2 [2]. Also, other arthropods, like ticks, have a similar trick and inject prostaglandins into their host while sucking blood [3]. Therefore, the salmon louse may do the same and suppress the immune system by injecting PGE2 into the salmon.
However, there is still lack of concrete evidence for this hypothesis. Therefore, in our new paper [4] we have tried to further investigate the role of prostaglandins by studying PGE2 and salmon louse genes that could be responsible for PGE2 synthesis, the prostaglandin E2 synthases (PGES). After an extensive search in the genome, we found in total three putative PGES’, two of these new and one already described [5]. When looking at their gene-expression, none of the PGES’ had a pattern that one would expect for a gene involved in the host-parasite interaction as none of the genes increased their expression levels immediate to or after infection, nor were the genes expressed in glands. Instead, they were expressed in reproductive tissues and intestine. And most importantly, when we knocked down the PGES genes by RNA-interference, no effects were observed on the infestation success nor the skin immune response.
But then, what is the function of prostaglandins in the salmon louse? When we knocked down another gene, which is known to result in oxidative stress in the louse [6], we saw that PGES genes were up regulated. Therefore, we concluded that the function of PGES is rather internal to the louse: related to stress response and reproduction.
In consequence, proving involvement of PGES or PGE2 in immune modulation might seem like a long shot. And even if PGE2 has an immune-modulative role, it is simply not a suitable target for intervention. The reason for this is: prostaglandins are compounds, not proteins, and as such the prostaglandins found in the salmon are surely chemically identical to those from the louse, and there might not be a good way to intervene without affecting the salmon as well.
In conclusion, we think it is about time to shift targets. One should keep in mind that there are more than 13,000 protein coding genes in LiceBase. Most of them have not been characterized in any way. Therefore, we are actively working on identification and characterization of novel factors within the project ModuLus to better understand the tricks of immune modulation, new knowledge that will pave the way for better management of this parasite.
