Leishmania donovani promastigotes evade the activation of mitogen-activated protein kinases p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase-1/2 during infection of naive macrophages
✍ Scribed by Charles Privé; Albert Descoteaux
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 178 KB
- Volume
- 30
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
The protozoan parasite Leishmania fails to activate naive macrophages for proinflammatory cytokines production, and selectively impairs signal transduction pathways in infected macrophages. Because mitogen-activated protein kinases (MAPK)-and NF-‹ B-dependent signaling pathways regulate proinflammatory cytokines release, we investigated their activation in mouse bone marrow-derived macrophages (BMM) exposed to Leishmania donovani promastigotes. In naive BMM, the parasite failed to induce the phosphorylation of p38 MAPK, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK)1/2, as well as the degradation of I ‹ B- § . The use of L. donovani mutants defective in the biosynthesis of lipophosphoglycan revealed that evasion of ERK1/2 activation requires surface expression of the repeating unit moiety of this virulence determinant. In IFN-+ -primed BMM, L. donovani promastigotes strongly induced the phosphorylation of p38 MAPK and ERK1/2, and the use of selective inhibitors for ERK (PD98059) and p38 MAPK (SB203580) revealed that both kinases are required for L. donovani-induced TNF- § but not NO 2 -release. Collectively, these data suggest that both p38 MAPK and ERK1/2 pathways participate in some Leishmaniainduced responses in IFN-+ -primed BMM. The ability of L. donovani promastigotes to avoid MAPK and NF-‹ B activation in naive macrophages may be part of the strategy evolved by this parasite to evade innate immune responses.