Macrophage migration inhibitory factor (MIF) plays a pivotal role in immunity against Salmonella typhimurium.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America - Year 2002, Vol 99, Issue 21
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 and Affiliations
Heidrun Koebernick, Leander Grode, John R David, Wolfgang Rohde, Michael S Rolph, Hans-Willi Mittrücker, Stefan H E Kaufmann
Keywords
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