title: Differential effect of Cryptococcus neoformans on the production of IL-12p40 and IL-10 by murine macrophages stimulated with lipopolysaccharide and gamma interferon.
abstract: In the present study, we examined the in vitro effect of Cryptococcus neoformans on the production of interleukin-12 (IL-12) and IL-10 by murine macrophages. At a dose of 1 x 10(5), 1 x 10(6) or 1 x 10(7) ml-1, a highly virulent strain of C. neoformans (strain YC-11) suppressed the production of IL-12p40 by a murine macrophage cell line, J774.1 stimulated with lipopolysaccharide (LPS) and interferon (IFN)-gamma, while the production of IL-10 was not inhibited, but rather slightly augmented. The suppression of IL-12p40 production did not change by neutralizing anti-IL-10 mAb. A direct contact of C. neoformans with macrophages was largely involved in this inhibitory effect, since placement of a 0.45 micron pore membrane between the organism and macrophages prevented such effect. On the other hand, the culture supernatant of YC-11 did not inhibit macrophage IL-12p40 production when used at a lower dose, which contained an equivalent amount of capsular polysaccharide to that in the supernatant of YC-11 cultured at 1 x 10(5) or 1 x 10(6) ml-1, although it showed a small suppression at higher doses. Our results suggest that C. neoformans may suppress the induction of Th1 responses by inhibiting macrophage IL-12 production predominantly through a direct contact-dependent mechanism and to a lesser extent by a certain soluble factor(s) released from this microorganism.
authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan. kawakami@med.u-ryukyu.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Kawakami
authors.forename: M H
authors.initials: MH
authors.lastname: Qureshi
authors.forename: Y
authors.initials: Y
authors.lastname: Koguchi
authors.forename: K
authors.initials: K
authors.lastname: Nakajima
authors.forename: A
authors.initials: A
authors.lastname: Saito
mesh_terms: D000818:Animals; D002460:Cell Line; D003453:Cryptococcosis / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000254:growth & development / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008172:Lung Diseases, Fungal / Q000382:microbiology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology*; D051379:Mice
chemical_list: D008070:Lipopolysaccharides; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma