Phagocytosis of Leishmania mexicana amastigotes by macrophages leads to a sustained suppression of IL-12 production.
Healing of leishmaniases is dependent on activation of parasitized macrophages (Mphi) by IFN-gamma, which is secreted by Leishmania-specific Th1 cells. IL-12 enhances IFN-gamma production by Th1 cells and is crucial for cure. The host cells of Leishmania sp., Mphi, are a main source of IL-12 in vivo. We report that infection of quiescent murine Mphi with L. mexicana or L. major amastigotes does not induce IL-12 production. Moreover, infection suppresses IL-12 secretion by Mphi activated by LPS, by CD40 cross-linking or cognate interaction with Th1 cells. IL-12 secretion is also suppressed in Mphi activated after phagocytosis of latex beads. Suppression is independent of engagement of CR3 or FcgammaR during phagocytosis, is not mediated by IL-10 and does not alter steady state IL-12p40 mRNA levels. In addition, suppression of IL-12 secretion does not depend on Mphi activation concurrent to infection. In contrast, NO production was not inhibited. Thus, Mphi effector functions are differentially affected and this may be a general effect of phagocytosis of non-activating particles. The possible implications of this effect on the infection are discussed.
Max-Planck-Institut für Biologie, Abteilung Membranbiochemie, Tübingen, Germany.
N
N
Weinheber
M
M
Wolfram
D
D
Harbecke
T
T
Aebischer
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001483:Base Sequence; D019013:CD40 Antigens / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005260:Female; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D007894:Leishmania mexicana / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis; D010587:Phagocytosis / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D017931:DNA Primers; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma