Induction of Host Protective Th1 Immune Response by Chemokines in Leishmania donovani‐infected BALB/c Mice

Scandinavian Journal of Immunology - Tập 66 Số 6 - Trang 671-683 - 2007
Ranadhir Dey1, Nivedita Majumder1, S. Majumdar1, Surajit Bhattacharjee1, Sayantan Banerjee2, Syamal Roy2, Shamik Majumdar1
1Department of Microbiology, Bose Institute, Kolkata
2Division of Immunology, Indian Institute of Chemical Biology, Kolkata, India

Tóm tắt

AbstractThe 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)‐1α 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‐1α 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‐β 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)‐γ, tumour necrosis factor‐α 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‐γ. These studies hypothesize a promising immuno‐prophylactic effect of chemokines against leishmaniasis by induction of Th1 cytokine release imparting a long‐term resistance.

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Scandinavian Journal of Immunology

Tập 66 Số 6

671-683

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