Phagocytosis of Leishmania mexicana amastigotes by macrophages leads to a sustained suppression of IL-12 production

Eur J Immunol. 1998 Aug;28(8):2467-77. doi: 10.1002/(SICI)1521-4141(199808)28:08<2467::AID-IMMU2467>3.0.CO;2-1.

Abstract

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.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Base Sequence
  • CD40 Antigens / metabolism
  • DNA Primers / genetics
  • Female
  • In Vitro Techniques
  • Interferon-gamma / pharmacology
  • Interleukin-12 / biosynthesis*
  • Interleukin-12 / genetics
  • Leishmania mexicana / immunology*
  • Leishmaniasis, Cutaneous / genetics
  • Leishmaniasis, Cutaneous / immunology
  • Leishmaniasis, Cutaneous / parasitology
  • Lipopolysaccharides / pharmacology
  • Macrophage Activation
  • Macrophages / immunology*
  • Macrophages / parasitology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Nitric Oxide / biosynthesis
  • Phagocytosis / immunology*
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins

Substances

  • Antibodies, Monoclonal
  • CD40 Antigens
  • DNA Primers
  • Lipopolysaccharides
  • RNA, Messenger
  • Recombinant Proteins
  • Interleukin-12
  • Nitric Oxide
  • Interferon-gamma