The protozoan parasite Trypanosoma brucei is the causative agent of the neglected tropical disease human African trypanosomiasis, otherwise known as sleeping sickness. Trypanosomes have evolved many immune evasion mechanisms in order to facilitate their own survival, as well as prolonging host survival to ensure completion of the parasitic life cycle. A key feature of the bloodstream form of T. brucei is the secretion of aromatic keto acids, which are metabolised from host amino acids. Here we describe an immunomodulatory role for one of these keto acids, indole-3-pyruvate (I3P). We demonstrate that I3P inhibits the production of prostaglandins (PGs) in activated macrophages. We also show that, despite the reduction in downstream PGs, I3P augments the expression of COX2. This increase in COX2 expression is mediated via activation of the aryl hydrocarbon receptor (AhR). However the increase in COX2 expression is of little functionality as we also provide evidence to suggest that I3P directly inhibits COX activity. This study therefore details an evasion strategy whereby a trypanosome-secreted metabolite potently inhibits macrophage-derived PGs, which might promote host and trypanosome survival.

The protozoan parasite _Trypanosoma brucei_ is the causative agent of the neglected tropical disease human African trypanosomiasis, otherwise known as sleeping sickness. Trypanosomes have evolved many immune evasion mechanisms in order to facilitate their own survival, as well as prolonging host survival to ensure completion of the parasitic life cycle. A key feature of the bloodstream form of _T. brucei_ is the secretion of aromatic keto acids, which are metabolised from host amino acids. Here we describe an immunomodulatory role for one of these keto acids, indole-3-pyruvate (I3P). We demonstrate that I3P inhibits the production of prostaglandins (PGs) in activated macrophages. We also show that, despite the reduction in downstream PGs, I3P augments the expression of COX2. This increase in COX2 expression is mediated via activation of the aryl hydrocarbon receptor (AhR). However the increase in COX2 expression is of little functionality as we also provide evidence to suggest that I3P directly inhibits COX activity. This study therefore details an evasion strategy whereby a trypanosome-secreted metabolite potently inhibits macrophage-derived PGs, which might promote host and trypanosome survival.

The trypanosome-derived metabolite indole-3-pyruvate inhibits prostaglandin production in macrophages by targeting COX2

Exploring the intricacies of host-pathogen communication is vital in order to understand why
some microbes persist within a host, while others are effectively cleared. As such,
host-pathogen communication is an urgent area of research underpinning human health
and disease, especially given the emerging concerns of antibiotic resistance.
Understanding host-pathogen pathways requires intricate knowledge in the fields of both
microbiology and immunology.

Living in a world of specialists, where scientists sometimes invest their whole career
studying one organism, a specific pathway or a protein, multidisciplinary discussions of
host-pathogen interactions are highly needed. This international conference will provide
such a forum for scientific exchange at the highest level, between scientists from different
research areas related to host-pathogen interactions, with the aim to trigger fruitful
collaborations addressing the urgent questions in the field.

This meeting has an additional special focus of bringing researchers from Ireland, Denmark
and Israel together to learn about cutting edge biology and form new collaborations.
Thus, the conference will be a showcase for the exciting and original research emanating
from these three small but innovative countries.