title: [Phagocytosis of Mycobacterium leprae down-regulates anti-microbial activity of murine macrophages against Mycobacterium intracellulare].
abstract: Patients with highly bacillated lepromatous leprosy (LL) essentially lack T cell-mediated immune responses specific to Mycobacterium leprae (ML) antigens, resulting in severely impaired host resistance to leprosy bacilli. Such type of immune unresponsiveness characteristic of LL patients is mainly attributable to markedly depressed T cell ability to activate/expand in response to ML antigens. In this study, we examined profiles of antimycobacterial activity of macrophages, which phagocytized leprosy bacilli, because there is another possibility that, in LL patients, host macrophages in the leprosy lesions are impaired in their antimicrobial activity due to their interaction with infected leprosy bacilli, particularly cellular events through binding with and/or internalization of the pathogens, thereby causing the reduction in host resistance to ML pathogens. The present study indicated the following. First, the anti-M. avium complex activity of murine peritoneal macrophages was significantly reduced when they had phagocytosed heat-killed leprosy bacilli. Second, infection of macrophages with leprosy bacilli did not affect macrophage-mediated suppressor activity against T cell proliferative response to Concanavalin A. These findings indicate that macrophage's intracellular signaling pathways that are up-regulated in response to phagocytosis of leprosy bacilli are linked to the signaling cascades participating in macrophage antimicrobial functions, but not cross-talk with those allowing the expression of macrophage's suppressor activity against T cell functions.
authors.affiliation: Department of Microbiology and Immunology, Shimane University School of Medicine, Izumo, Shimane, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tatano
authors.forename: Chiaki
authors.initials: C
authors.lastname: Sano
authors.forename: Masako
authors.initials: M
authors.lastname: Emori
authors.forename: Hajime
authors.initials: H
authors.lastname: Saito
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Sato
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shimizu
authors.forename: Haruaki
authors.initials: H
authors.lastname: Tomioka
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology*; D006801:Humans; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D015269:Mycobacterium avium Complex / Q000276:immunology*; D009166:Mycobacterium leprae / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D017382:Reactive Oxygen Species