Leishmania donovani infection induce Extracellular signal -regulated kinase 1/2 (ERK1/2) mediated lipid droplet generation in macrophages

Recently unfolded mechanisms showed lipid droplet helps in pathogen survival and paralyzes host immune response. In the present study, we showed the extent of lipid droplet(LD) generation in Leishmania donovani infection, the signaling involved, and their function concerning pathogenicity. RAW 264.7 and J774A.1 cells were used to infect with L. donovani and then flow cytometry and confocal microscopy were used to detect lipid droplet generation and subsequent assays. In this study, we showed that L. donovani AG83 (AG83/MHOM/1983) triggers lipid droplet formation in macrophages in a time-dependent manner. We provide novel insight into the signaling molecules which is responsible for LD accumulation. Interestingly, LPG deficient attenuated Leishmania strain UR6 (UR6/MHOM/1978) failed to fuel LD generation. But inhibition of phagosome maturation drastically stimulates LD accumulation in UR6 infected M Phi s. Aspirin treatment in AG83 infected M Phi s does not only lower LD load but also favors phagolysosome biogenesis and corrects cytokine balance. Employing strategies to circumvent halt in phagosome maturation using drugs that manipulate lipid droplet generation could be used as a therapeutic tool to resist parasite growth in the early hour of infection.

Automated summary

In this study, the researchers investigated the generation and function of lipid droplets (LD) in Leishmania donovani infection. They found that infection with L. donovani triggers LD formation in macrophages in a time-dependent manner. The signaling molecules responsible for LD accumulation were also identified. Moreover, inhibition of phagosome maturation enhanced LD accumulation in certain strains of Leishmania. Treatment with aspirin not only reduced LD load but also improved phagolysosome biogenesis and cytokine balance. These findings suggest that manipulating LD generation could be a potential therapeutic strategy against parasite growth in the early stages of infection.