Infection with L. donovani affects mainly visceral organs. Importantly, the parasitic load differs in different visceral organs; therefore there is a need to understand the organ specific immune regulation, particularly in the spleen and liver. Comparative studies between these organs in Leishmania infected hamster (Mesocricetus auratus) are lacking. Our study highlights the importance of
eicosanoids in the organ specific pathology of
visceral leishmaniasis. Among other immune cells, macrophages (mφ) which harbor Leishmania parasite are major producers of
eicosanoids. In this study, we intend to explore linkage between organ specific immune response and
eicosanoids. We suggest that
eicosanoids (early immune modulators) and their organ specific expressions, possibly tune the outcome of mφ differently at different sites. We have observed that liver showed better containment of parasitic load than spleen, where we have found higher expression of
5-lipoxygenase (5-LO)
enzyme along with
IL-12 and iNOS. However, in spleen,
enzymes of the
PGE2 pathway i.e.
PGE2 synthases (cytosolic and microsomal) along with
IL-10 were predominantly higher. To further corroborate our findings, in vitro assays were carried out using purified
eicosanoids (
LTB4 and
PGE2) and the inhibitors of these pathways. Findings establish that the
5-lipoxygenase pathway (i.e.
LTB4) is anti-parasitic and its inhibition increases the parasitic load (qPCR based
kDNA detection). On the contrary, PGES pathway (i.e.
PGE2) supports establishment of
infection in mφ. Taken together, 5-LO pathway plays a protective role in liver during L. donovani
infection. However, the PGES pathway favors the parasite growth, particularly in the spleen at a later stage.