Zutshi, S and Sarode, AY and Ghosh, SK and Jha, MK and Sudan, R and Kumar, S and Sadhale, LP and Roy, S and Saha, B (2021) LmjF.36.3850, a novel hypothetical Leishmania major protein, contributes to the infection. In: Immunology, 163 (4). pp. 460-477.
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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-TEM 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.
| Item Type: | Journal Article |
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| Publication: | Immunology |
| Publisher: | John Wiley and Sons Inc |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Keywords: | DNA vaccine; immunization; Leishmania; LmjF.36.3850; virulence |
| Department/Centre: | Division of Biological Sciences > Microbiology & Cell Biology |
| Date Deposited: | 05 Jun 2023 10:59 |
| Last Modified: | 05 Jun 2023 10:59 |
| URI: | https://eprints.iisc.ac.in/id/eprint/81780 |
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