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- Title
Induction of host protective Th1 immune response by chemokines in Leishmania donovani-infected BALB/c mice.
- Authors
Dey, R; Majumder, N; Bhattacharyya Majumdar, S; Bhattacharjee, S; Banerjee, S; Roy, S; Majumdar, S
- Abstract
The resolution from leishmanial infection is dependent on the coordinated interactions between the components of the cell mediated immune system and the activation of T-cell population into appropriate cytokine production and the activation of macrophages. Earlier reports established that C-C chemokines particularly macrophage inflammatory protein (MIP)-1alpha and macrophage chemoattractant protein (MCP)-1 restrict the parasitic burden via the regulation of impaired protein kinase C (PKC) signalling and induction of free-radical generation in murine leishmaniasis. This study explored the role of MIP-1alpha and MCP-1 in the induction of T helper 1 (Th1) immune response and suppression of T helper 2 (Th2) response in Leishmania donovani-infected BALB/c mice. These chemokines induced the known pro-inflammatory cytokine interleukin (IL)-12 secretion and inhibited the secretion of anti-inflammatory cytokines IL-10 and transforming growth factor-beta in infected macrophages. Impaired antigen presentation capability of infected macrophages was also restored by the chemokine treatment. C-C chemokine treatment resulted in reduced levels of mRNA expression of IL-10, but increased levels of mRNA expression of IL-12p40, interferon (IFN)-gamma, tumour necrosis factor-alpha and inducible nitric oxide synthase in both liver mononuclear cells as well as in splenocytes, reflecting a switch of CD4+ differentiation from Th2 to Th1. Flow cytometric analysis of infected spleen cells suggested that C-C chemokine treatment enhances the CD4+ T cells to produce increased levels of IFN-gamma. These studies hypothesize a promising immuno-prophylactic effect of chemokines against leishmaniasis by induction of Th1 cytokine release imparting a long-term resistance.
- Publication
Scandinavian journal of immunology, 2007, Vol 66, Issue 6, p671
- ISSN
1365-3083
- Publication type
Journal Article
- DOI
10.1111/j.1365-3083.2007.02025.x