title: Macrophage migration inhibitory factor (MIF) plays a pivotal role in immunity against Salmonella typhimurium.
abstract: The cytokine macrophage migration inhibitory factor (MIF) exerts a multitude of biological functions. Notably, it induces inflammation at the interface between the immune system and the hypothalamus-pituitary-adrenal stress axis. The role of MIF in infectious diseases is not understood completely. Here, we show that MIF-deficient (MIF(-/-)) knockout mice fail to control an infection with wild-type Salmonella typhimurium. Increased susceptibility was accompanied by a reduced Th1 response, demonstrated by decreased levels of IL-12, IFNgamma, and tumor necrosis factor alpha. In Salmonella-infected MIF(-/-) mice, levels of IL-1beta were markedly increased. Additionally, infected MIF(-/-) mice showed elevated serum levels of nitric oxide and corticosterone as compared with control mice. Our results point to MIF as a key mediator in the host response to S. typhimurium. MIF not only promotes development of a protective Th1 response but ameliorates disease by altering levels of reactive nitrogen intermediates and corticosteroid hormones, which both exert immunosuppressive functions.
authors.affiliation: Max Planck Institute for Infection Biology, Department of Immunology, Schumannstrasse 20/21, 10117 Berlin, Germany.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Koebernick
authors.forename: Leander
authors.initials: L
authors.lastname: Grode
authors.forename: John R
authors.initials: JR
authors.lastname: David
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rohde
authors.forename: Michael S
authors.initials: MS
authors.lastname: Rolph
authors.forename: Hans-Willi
authors.initials: HW
authors.lastname: Mittrücker
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000097:blood; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008263:Macrophage Migration-Inhibitory Factors / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis; D012480:Salmonella Infections / Q000097:blood / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology* / Q000472:pathogenicity; D018417:Th1 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D018836:Inflammation Mediators; D008263:Macrophage Migration-Inhibitory Factors; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma; D003345:Corticosterone