Leishmania donovani infection of human myeloid dendritic cells leads to a Th1 response in CD4+ T cells from healthy donors and patients with kala-azar.
The role played by dendritic cells (DCs) in Leishmania donovani infection is poorly understood. Here, we report that L. donovani amastigotes efficiently infect human peripheral-blood monocyte-derived DCs. Opsonization with normal human serum enhanced the infectivity of amastigotes and promastigotes only marginally. Surface attachment versus internalization was distinguished by incubation of DCs with live, fluorescein isothiocyanate-labeled parasites, followed by quenching with crystal violet. Infection with amastigotes was accompanied by DC maturation, as was evident from the up-regulation of maturation-associated cell-surface markers, the nuclear translocation of RelB, and the release of cytokines. Amastigote-primed DCs produced inflammatory cytokines in response to subsequent treatment with interferon- gamma or anti-CD40 monoclonal antibody. When cocultured, amastigote-infected DCs induced T helper cell type 1 (Th1) responses both in naive allogeneic CD4(+) T cells and in autologous CD4(+) T cells from patients with kala-azar and up-regulated the expression of T-bet. Our data reveal that infection with L. donovani amastigotes induces a Th1 cytokine milieu in both DCs and T cells.
Ghosh
Monidipa
M
Department of Immunology, Indian Institute of Chemical Biology, Kolkata, India.
Mandal
Labanya
L
Maitra
Sudipta
S
Rakshit
Srabanti
S
Paul
Kausik
K
Bagchi
Jayashree
J
Ganguly
Dipyaman
D
Pal
Chiranjib
C
Bandyopadhyay
Santu
S
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D006224:Cricetinae; D003713:Dendritic Cells / Q000276:immunology* / Q000469:parasitology*; D050990:GATA3 Transcription Factor / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007893:Leishmania donovani / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008018:Life Cycle Stages; D008213:Lymphocyte Activation; D008647:Mesocricetus; D022423:Myeloid Cells / Q000276:immunology / Q000469:parasitology; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D000098815:T-bet Transcription Factor
D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor