knockout parasites promote M1-polarizing metabolic changes.

Leishmaniasis is a tropical disease prevalent in 90 countries. Presently, there is no approved vaccine for human use. We developed a live attenuated strain as a vaccine candidate that showed excellent efficacy, characterized by reduced Th2 and enhanced Th1 responses in C57BL/6 and BALB/c mice, respectively, compared to wild-type WT infection. Toward understanding the immune mechanisms of protection, we applied untargeted mass spectrometric analysis to and WT infections. Data showed enrichment of the pentose phosphate pathway (PPP) in ears immunized with versus naive and WT infection. PPP promotes M1 polarization in macrophages, suggesting a switch to a pro-inflammatory phenotype following inoculation. Accordingly, PPP inhibition in macrophages infected with reduced the production of nitric oxide and interleukin (IL)-1β, hallmarks of classical activation. Overall, our study revealed the immune regulatory mechanisms that may be critical for the induction of protective immunity.