Macrophage migration inhibitory factor and innate immune responses to bacterial infections

ABSTRACT Nosocomial infections in immune-suppressed patients are a widespread problem in intensive care medicine. Such patients are highly susceptible to infections because their immune defenses are impaired and, therefore, unable to adequately combat invading microorganisms. To investigate the problem of sepsis-induced immune suppression, we used a model in which mice developed sublethal peritonitis induced by cecal ligation and puncture (CLP). Two days after CLP mice were in an immune-suppressed state, as measured by impaired capacity to produce tumor necrosis factor (TNF) and enhanced susceptibility to bacterial infections. Since macrophage migration inhibitory factor (MIF) is a critical mediator of septic shock by modulation of innate immune responses, the role of MIF in sepsis-induced immune suppression was analyzed. Neutralization of endogenous MIF further enhanced susceptibility to bacterial superinfection after CLP. Conversely, treatment with recombinant human MIF before the bacterial superinfection protected the animals. MIF treatment reconstituted the impaired capacity to produce proinflammatory cytokines, such as TNF and interleukin-6. This study indicates that MIF might be able to ameliorate the sepsis-induced immune suppression by reenabling the organism to react adequately to a secondary bacterial challenge.

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Macrophage migration inhibitory factor promotes innate immune responses by suppressing glucocorticoid-induced expression of mitogen-activated protein kinase phosphatase-1

European Journal of Immunology ◽

10.1002/eji.200535413 ◽

2005 ◽

Vol 35 (12) ◽

pp. 3405-3413 ◽

Cited By ~ 133

Author(s):

Thierry Roger ◽

Anne-Laure Chanson ◽

Marlies Knaup-Reymond ◽

Thierry Calandra

Keyword(s):

Protein Kinase ◽

Immune Responses ◽

Migration Inhibitory Factor ◽

Macrophage Migration Inhibitory Factor ◽

Innate Immune ◽

Mitogen Activated Protein Kinase ◽

Macrophage Migration ◽

Innate Immune Responses ◽

Induced Expression ◽

Mitogen Activated Protein

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Macrophage Migration Inhibitory Factor Reduces the Growth of Virulent Mycobacterium tuberculosis in Human Macrophages

Infection and Immunity ◽

10.1128/iai.73.6.3783-3786.2005 ◽

2005 ◽

Vol 73 (6) ◽

pp. 3783-3786 ◽

Cited By ~ 33

Author(s):

Mauro Oddo ◽

Thierry Calandra ◽

Richard Bucala ◽

Pascal R. A. Meylan

Keyword(s):

Mycobacterium Tuberculosis ◽

Migration Inhibitory Factor ◽

Innate Immune System ◽

Host Response ◽

Macrophage Migration Inhibitory Factor ◽

Bacterial Infections ◽

Innate Immune ◽

Inhibitory Factor ◽

Macrophage Migration ◽

Human Macrophages

ABSTRACT Macrophage migration inhibitory factor (MIF) is a key mediator of the innate immune system and plays a crucial role in the host response to bacterial infections. Its role in immunity to intracellular pathogens has not been well studied. Here, we show that MIF released by infected human macrophages inhibits the growth of virulent Mycobacterium tuberculosis.

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