Induction of host protective Th1 immune response by chemokines in Leishmania donovani-infected BALB/c mice.
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.
Dey
R
R
Department of Microbiology, Bose Institute, Kolkata, India.
Majumder
N
N
Bhattacharyya Majumdar
S
S
Bhattacharjee
S
S
Banerjee
S
S
Roy
S
S
Majumdar
S
S
D000818:Animals; D002450:Cell Communication; D002454:Cell Differentiation; D018932:Chemokine CCL2 / Q000276:immunology; D054405:Chemokine CCL3 / Q000276:immunology; D018925:Chemokines / Q000276:immunology*; D006224:Cricetinae; D005434:Flow Cytometry; D006790:Host-Parasite Interactions / Q000276:immunology*; D007893:Leishmania donovani / Q000276:immunology* / Q000469:parasitology; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology* / Q000469:parasitology*; D018418:Th2 Cells / Q000276:immunology
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D018925:Chemokines; D012333:RNA, Messenger