title: Mycobacterium avium infection of macrophages results in progressive suppression of interleukin-12 production in vitro and in vivo.
abstract: Interleukin-12 (IL-12) has been shown to have an important role in the host defense against Mycobacterium avium. We sought to determine if human monocyte-derived macrophages produce IL-12 upon M. avium infection. Although IL-12 can be measured in supernatants of M. avium-infected macrophages at 24, 48, and 72 h following infection, intracellular staining showed that 24 to 48 h after infection, IL-12 was synthesized chiefly by uninfected macrophages in the monolayer, suggesting that M. avium infection inhibits IL-12 production. In addition, the data also suggest that the longer macrophage monolayers were infected, the less IL-12 they were able to produce. Stimulation of macrophages with IFN-gamma prior to infection with M. avium resulted in greater production of IL-12 compared with unstimulated macrophages. Culture supernatant of M. avium-infected macrophage monolayers, but not control macrophages, partially inhibited IL-12 production by IFN-gamma-stimulated macrophages. This partial inhibition was not reversed by anti-interleukin-10 (anti-IL-10) and anti-transforming growth factor beta 1 (anti-TGF beta 1)-neutralizing antibodies. M. avium infection of macrophages in vitro also suppressed IL-12 synthesis induced by Listeria monocytogenes infection. Immunohistochemistry staining of spleen of infected mice showed that IL-12 production by splenic macrophages was more pronounced in the beginning of the infection but decreased later. Our data indicate that M. avium infection of macrophages suppresses IL-12 production by infected cells and that the suppression was not a result of the presence of IL-10 and TGF beta 1 in the culture supernatant.
authors.affiliation: Laboratory of Bacterial Pathogenesis, Kuzell Institute for Arthritis and Infectious Diseases, California Pacific Medical Center Research Institute, San Francisco, California 94115, USA.
authors.forename: Dirk
authors.initials: D
authors.lastname: Wagner
authors.forename: Felix J
authors.initials: FJ
authors.lastname: Sangari
authors.forename: Sang
authors.initials: S
authors.lastname: Kim
authors.forename: Mary
authors.initials: M
authors.lastname: Petrofsky
authors.forename: Luiz E
authors.initials: LE
authors.lastname: Bermudez
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D009162:Mycobacterium avium / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*
chemical_list: D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D018664:Interleukin-12