Open AccessMacrophage migration inhibitory factor (MIF) plays a pivotal role in immunity againstSalmonella typhimurium
Author(s) -
Heidrun Koebernick,
Leander Grode,
John R. David,
Wolfgang Rohde,
Michael S. Rolph,
HansWilli Mittrücker,
Stefan H. E. Kaufmann
Publication year - 2002
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.212488699
Subject(s) - macrophage migration inhibitory factor , immune system , tumor necrosis factor alpha , cytokine , inflammation , macrophage , immunology , salmonella , biology , nitric oxide , microbiology and biotechnology , endocrinology , medicine , bacteria , in vitro , biochemistry , genetics
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.