Mevalonate kinase of Leishmania donovani promotes its survival and plays a pivotal role in pathogenesis.
Exp Parasitol
; 263-264: 108800, 2024.
Article
in En
| MEDLINE
| ID: mdl-39043326
ABSTRACT
The infectivity of Leishmania is determined by its ability to invade and evade host and its thriving capacity within the macrophage. Our study revealed the role of Leishmania donovani mevalonate kinase (MVK), an enzyme of mevalonate pathway in visceral leishmaniasis pathogenesis. Peritoneal exudate cells (PEC)-derived macrophages from BALB/c mice were infected with wild type (WT), MVK over expressing (MVK OE) and knockdown (KD) parasites and MVK OE parasites were found to be more infective than WT and MVK KD parasites. Incubation of macrophages with MVK OE parasites declined inducible nitric oxide synthase (iNOS) expression as well as nitric oxide (NO) production, both by 2 times in comparison to WT parasites. Moreover, â¼3 fold increase in Arginase1 expression indicated that MVK might induce polarization of macrophage towards M2, favouring the survival of parasite within the macrophages. Post 24 h infection of the macrophages with mutant strains, the levels of different cytokines (TNF-α, IL-12, IL-10 and IFN-γ) were measured. Infection of macrophages with MVK OE parasites showed an increase in the level of anti-inflammatory cytokine IL-10 while infection with MVK KD parasites exhibited an increase in the level of pro-inflammatory cytokines TNF-α, IL-12, and IFN-γ. Hence, Leishmania donovani mevalonate kinase (LdMVK) modulates macrophage functions and has a significant role in pathogenesis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Leishmania donovani
/
Cytokines
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Phosphotransferases (Alcohol Group Acceptor)
/
Macrophages, Peritoneal
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Nitric Oxide Synthase Type II
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Leishmaniasis, Visceral
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Mice, Inbred BALB C
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Nitric Oxide
Limits:
Animals
Language:
En
Journal:
Exp Parasitol
Year:
2024
Document type:
Article
Affiliation country:
India
Country of publication:
United States