Macrophage migration inhibitory factor (MIF) plays a pivotal role in immunity against Salmonella typhimurium
Standard
Macrophage migration inhibitory factor (MIF) plays a pivotal role in immunity against Salmonella typhimurium. / Koebernick, Heidrun; Grode, Leander; David, John R; Rohde, Wolfgang; Rolph, Michael S; Mittrücker, Hans-Willi; Kaufmann, Stefan H E.
in: P NATL ACAD SCI USA, Jahrgang 99, Nr. 21, 15.10.2002, S. 13681-6.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Macrophage migration inhibitory factor (MIF) plays a pivotal role in immunity against Salmonella typhimurium
AU - Koebernick, Heidrun
AU - Grode, Leander
AU - David, John R
AU - Rohde, Wolfgang
AU - Rolph, Michael S
AU - Mittrücker, Hans-Willi
AU - Kaufmann, Stefan H E
PY - 2002/10/15
Y1 - 2002/10/15
N2 - 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.
AB - 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.
KW - Animals
KW - Corticosterone
KW - Inflammation Mediators
KW - Interferon-gamma
KW - Interleukin-12
KW - Macrophage Migration-Inhibitory Factors
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Nitric Oxide
KW - Salmonella Infections
KW - Salmonella typhimurium
KW - Th1 Cells
KW - Tumor Necrosis Factor-alpha
U2 - 10.1073/pnas.212488699
DO - 10.1073/pnas.212488699
M3 - SCORING: Journal article
C2 - 12271144
VL - 99
SP - 13681
EP - 13686
JO - P NATL ACAD SCI USA
JF - P NATL ACAD SCI USA
SN - 0027-8424
IS - 21
ER -