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A Brugia malayi Homolog of Macrophage Migration Inhibitory Factor Reveals an Important Link Between Macrophages and
 

Summary: A Brugia malayi Homolog of Macrophage Migration Inhibitory
Factor Reveals an Important Link Between Macrophages and
Eosinophil Recruitment During Nematode Infection1
Franco H. Falcone,2,3
P'ng Loke,2,4
Xingxing Zang,4
Andrew S. MacDonald,5
Rick M. Maizels,
and Judith E. Allen6
Infections with the helminth parasite Brugia malayi share many key features with Th2-mediated allergic diseases, including
recruitment of eosinophils. We have investigated the dynamics of inflammatory cell recruitment under type 2 cytokine conditions
in mice infected with B. malayi. Among the cells recruited to the site of infection is a novel population of "alternatively activated"
macrophages that ablate cell proliferation and enhance Th2 differentiation. By profiling gene expression in this macrophage
population, we found a dramatic up-regulation of a recently described eosinophil chemotactic factor, eosinophil chemotactic
factor-L/Ym1, representing over 9% of clones randomly selected from a cDNA library. Because B. malayi is known to secrete
homologs (Bm macrophage migration inhibitory factor (MIF)-1 and -2) of the human cytokine MIF, we chose to investigate the
role this cytokine mimic may play in the development of the novel macrophage phenotype observed during infection. Strikingly,
administration of soluble recombinant Bm-MIF-1 was able to reproduce the effects of live parasites, leading both to the up-
regulation of Ym1 by macrophages and a marked recruitment of eosinophils in vivo. Because activity of Bm-MIF-1 is dependent
upon an amino-terminal proline, this residue was mutated to glycine; the resultant recombinant (Bm-MIF-1G) was unable to

  

Source: Allen, Judith - School of Biological Sciences, University of Edinburgh
MacDonald, Andrew - Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh
Maizels, Rick - School of Biological Sciences, University of Edinburgh

 

Collections: Biology and Medicine; Environmental Sciences and Ecology