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- W3136703294 abstract "Abstract Leishmania is a protozoan parasite that resides in mammalian macrophages and inflicts the disease known as leishmaniasis. Although prevalent in 88 countries, an anti‐leishmanial vaccine remains elusive. While comparing the virulent and avirulent L . major transcriptomes by microarray, PCR and functional analyses for identifying a novel virulence‐associated gene, we identified LmjF.36.3850, a hypothetical protein significantly less expressed in the avirulent parasite and without any known function. Motif search revealed that LmjF.36.3850 protein shared phosphorylation sites and other structural features with sucrose non‐fermenting protein (Snf7) that shuttles virulence factors. LmjF.36.3850 was predicted to bind diacylglycerol (DAG) with energy value similar to PKCα and PKCβ, to which DAG is a cofactor. Indeed, 1‐oleoyl‐2‐acetyl‐sn‐glycerol (OAG), a DAG analogue, enhanced the phosphorylation of PKCα and PKCβI. We cloned LmjF.36.3850 gene in a mammalian expression vector and primed susceptible BALB/c mice followed by challenge infection. We observed a higher parasite load, comparable antibody response and higher anti‐inflammatory cytokines such as IL‐4 and IL‐10, while expression of major anti‐leishmanial cytokine, IFN‐γ, remained unchanged in LmjF.36.3850‐vaccinated mice. CSA restimulated LN cells from vaccinated mice after challenge infection secreted comparable IL‐4 and IL‐10 but reduced IFN‐γ, as compared to controls. These observations suggest a skewed Th2 response, diminished IFN‐γ secreting Th1‐T EM cells and increased central and effector memory subtype of Th2, Th17 and Treg cells in the vaccinated mice. These data indicate that LmjF.36.3850 is a plausible virulence factor that enhances disease‐promoting response, possibly by interfering with PKC activation and by eliciting disease‐promoting T cells." @default.
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- W3136703294 date "2021-04-26" @default.
- W3136703294 modified "2023-09-27" @default.
- W3136703294 title "LmjF.36.3850, a novel hypothetical Leishmania major protein, contributes to the infection" @default.
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- W3136703294 doi "https://doi.org/10.1111/imm.13331" @default.
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