Weinheber N, Wolfram M, Harbecke D, Aebischer T
Max-Planck-Institut für Biologie, Abteilung Membranbiochemie, Tübingen, Germany.
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.
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.
利什曼病的治愈依赖于由利什曼原虫特异性Th1细胞分泌的IFN-γ对被寄生巨噬细胞（Mphi）的激活。IL-12可增强Th1细胞产生IFN-γ，对治愈至关重要。利什曼原虫的宿主细胞Mphi是体内IL-12的主要来源。我们报道，用墨西哥利什曼原虫或硕大利什曼原虫无鞭毛体感染静止的小鼠Mphi不会诱导IL-12的产生。此外，感染会抑制由LPS激活、通过CD40交联或与Th1细胞的同源相互作用激活的Mphi分泌IL-12。在吞噬乳胶珠后被激活的Mphi中，IL-12的分泌也受到抑制。抑制作用与吞噬过程中CR3或FcγR的结合无关，不是由IL-10介导的，也不会改变稳态IL-12p40 mRNA水平。此外，IL-12分泌的抑制不依赖于与感染同时发生的Mphi激活。相反，NO的产生未受抑制。因此，Mphi效应功能受到不同影响，这可能是非激活颗粒吞噬作用的普遍效应。本文讨论了这种效应对感染可能产生的影响。
