scholarly journals Functional Characterization of the Plasmodium falciparum and P. berghei Homologues of Macrophage Migration Inhibitory Factor

2006 ◽  
Vol 75 (3) ◽  
pp. 1116-1128 ◽  
Author(s):  
Kevin D. Augustijn ◽  
Robert Kleemann ◽  
Joanne Thompson ◽  
Teake Kooistra ◽  
Carina E. Crawford ◽  
...  
Keyword(s):  
Immune Responses ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Functional Characterization ◽  
Inhibitory Factor ◽  
Mammalian Host ◽  
Mosquito Vector ◽  
Macrophage Migration ◽  
Human Embryonic Kidney Cells

ABSTRACT Macrophage migration inhibitory factor (MIF) is a mammalian cytokine that participates in innate and adaptive immune responses. Homologues of mammalian MIF have been discovered in parasite species infecting mammalian hosts (nematodes and malaria parasites), which suggests that the parasites express MIF to modulate the host immune response upon infection. Here we report the first biochemical and genetic characterization of a Plasmodium MIF (PMIF). Like human MIF, histidine-tagged purified recombinant PMIF shows tautomerase and oxidoreductase activities (although the activities are reduced compared to those of histidine-tagged human MIF) and efficiently inhibits AP-1 activity in human embryonic kidney cells. Furthermore, we found that Plasmodium berghei MIF is expressed in both a mammalian host and a mosquito vector and that, in blood stages, it is secreted into the infected erythrocytes and released upon schizont rupture. Mutant P. berghei parasites lacking PMIF were able to complete the entire life cycle and exhibited no significant changes in growth characteristics or virulence features during blood stage infection. However, rodent hosts infected with knockout parasites had significantly higher numbers of circulating reticulocytes. Our results suggest that PMIF is produced by the parasite to influence host immune responses and the course of anemia upon infection.

scholarly journals Structural and Functional Characterization of a Macrophage Migration Inhibitory Factor Homologue from the Marine CyanobacteriumProchlorococcus marinus,

Biochemistry ◽  
2010 ◽  
Vol 49 (35) ◽  
pp. 7572-7581 ◽  
Author(s):  
Anna A. Wasiel ◽  
Henriëtte J. Rozeboom ◽  
Doreen Hauke ◽  
Bert-Jan Baas ◽  
Ellen Zandvoort ◽  
...  
Keyword(s):  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Functional Characterization ◽  
Inhibitory Factor ◽  
Macrophage Migration

scholarly journals High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates

2016 ◽  
Vol 113 (8) ◽  
pp. E997-E1005 ◽  
Author(s):  
Thierry Roger ◽  
Anina Schneider ◽  
Manuela Weier ◽  
Fred C. G. J. Sweep ◽  
Didier Le Roy ◽  
...  
Keyword(s):  
Immune Responses ◽  
Migration Inhibitory Factor ◽  
Neonatal Sepsis ◽  
Defense Mechanisms ◽  
Macrophage Migration Inhibitory Factor ◽  
Severe Infection ◽  
Mechanistic Explanation ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Newborn Mice

The vulnerability to infection of newborns is associated with a limited ability to mount efficient immune responses. High concentrations of adenosine and prostaglandins in the fetal and neonatal circulation hamper the antimicrobial responses of newborn immune cells. However, the existence of mechanisms counterbalancing neonatal immunosuppression has not been investigated. Remarkably, circulating levels of macrophage migration inhibitory factor (MIF), a proinflammatory immunoregulatory cytokine expressed constitutively, were 10-fold higher in newborns than in children and adults. Newborn monocytes expressed high levels of MIF and released MIF upon stimulation with Escherichia coli and group B Streptococcus, the leading pathogens of early-onset neonatal sepsis. Inhibition of MIF activity or MIF expression reduced microbial product-induced phosphorylation of p38 and ERK1/2 mitogen-activated protein kinases and secretion of cytokines. Recombinant MIF used at newborn, but not adult, concentrations counterregulated adenosine and prostaglandin E2-mediated inhibition of ERK1/2 activation and TNF production in newborn monocytes exposed to E. coli. In agreement with the concept that once infection is established high levels of MIF are detrimental to the host, treatment with a small molecule inhibitor of MIF reduced systemic inflammatory response, bacterial proliferation, and mortality of septic newborn mice. Altogether, these data provide a mechanistic explanation for how newborns may cope with an immunosuppressive environment to maintain a certain threshold of innate defenses. However, the same defense mechanisms may be at the expense of the host in conditions of severe infection, suggesting that MIF could represent a potential attractive target for immune-modulating adjunctive therapies for neonatal sepsis.

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