Two waves of antigen-containing dendritic cells in vivo in experimental Leishmania major infection.
Dendritic cells (DC) can induce Th1 cell differentiation by producing IL-12. In experimental infection with Leishmania major, DC could differently respond to infection and induce Th1 cells in C57BL/6 but not BALB/c mice, and thus determine the resistance or susceptibility of these mice. We characterized L. major antigen-containing DC in vivo in draining lymph nodes of both strains. Conventional experimental infection is shown to result in two waves of these DC and our data argue against a relevant genetic difference in the DC initiating the anti-parasite Th cell response in these mice. In both strains the first wave of DC presented L. major antigens but was not infected, produced IL-12 but induced disease-mediating Th2 cells upon adoptive transfer. In contrast to current belief, this response was therefore not initiated by infected DC, which were only detected in the second wave. The kinetics of the two waves suggests that DC turnover has an important impact on antigen presentation during infections with complex pathogens.
Max-Planck-Institut für Infektionsbiologie, Abteilung Molekulare Biologie, Berlin, Germany.
Ana Clara
AC
Misslitz
Deutsches Rheumaforschungszentrum, Berlin, Germany.
Kerstin
K
Bonhagen
Max-Planck-Institut für Biologie, Abteilung Membranbiochemie, Tübingen, Germany.
Dorothee
D
Harbecke
Max-Planck-Institut für Infektionsbiologie, Abteilung Molekulare Biologie, Berlin, Germany.
Christoph
C
Lippuner
Deutsches Rheumaforschungszentrum, Berlin, Germany.
Thomas
T
Kamradt
Max-Planck-Institut für Infektionsbiologie, Abteilung Molekulare Biologie, Berlin, Germany.
Toni
T
Aebischer
D000818:Animals; D017951:Antigen Presentation; D000953:Antigens, Protozoan / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000469:parasitology; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents; D018664:Interleukin-12 / Q000096:biosynthesis; D007700:Kinetics; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D008164:Luminescent Proteins / Q000032:analysis; D008198:Lymph Nodes / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018418:Th2 Cells / Q000276:immunology
D000953:Antigens, Protozoan; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D018664:Interleukin-12