| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh, United Kingdom
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 induce Ym1 transcription in macrophages or to mediate the recruitment of eosinophils. These data suggest that macrophages may provide a crucial link between helminth parasites, their active cytokine mimics, and the recruitment of eosinophils in infection.
This article has been cited by other articles:
|
|
 |
|
  S. Donnelly, C. M. Stack, S. M. O'Neill, A. A. Sayed, D. L. Williams, and J. P. Dalton Helminth 2-Cys peroxiredoxin drives Th2 responses through a mechanism involving alternatively activated macrophages FASEB J, November 1, 2008; 22(11): 4022 - 4032. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. S. King, A. M. Knorn, C. Ohnmacht, and D. Voehringer Accumulation of Effector CD4 T Cells during Type 2 Immune Responses Is Negatively Regulated by Stat6 J. Immunol., January 15, 2008; 180(2): 754 - 763. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Loke, I. Gallagher, M. G. Nair, X. Zang, F. Brombacher, M. Mohrs, J. P. Allison, and J. E. Allen Alternative Activation Is an Innate Response to Injury That Requires CD4+ T Cells to be Sustained during Chronic Infection J. Immunol., September 15, 2007; 179(6): 3926 - 3936. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Cho, B. F. Jones, J. J. Vermeire, L. Leng, L. DiFedele, L. M. Harrison, H. Xiong, Y.-K. A. Kwong, Y. Chen, R. Bucala, et al. Structural and Functional Characterization of a Secreted Hookworm Macrophage Migration Inhibitory Factor (MIF) That Interacts with the Human MIF Receptor CD74 J. Biol. Chem., August 10, 2007; 282(32): 23447 - 23456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Voehringer, N. van Rooijen, and R. M. Locksley Eosinophils develop in distinct stages and are recruited to peripheral sites by alternatively activated macrophages J. Leukoc. Biol., June 1, 2007; 81(6): 1434 - 1444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. D. Augustijn, R. Kleemann, J. Thompson, T. Kooistra, C. E. Crawford, S. E. Reece, A. Pain, A. H. G. Siebum, C. J. Janse, and A. P Waters Functional Characterization of the Plasmodium falciparum and P. berghei Homologues of Macrophage Migration Inhibitory Factor Infect. Immun., March 1, 2007; 75(3): 1116 - 1128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Nair, K. J. Guild, and D. Artis Novel Effector Molecules in Type 2 Inflammation: Lessons Drawn from Helminth Infection and Allergy J. Immunol., August 1, 2006; 177(3): 1393 - 1399. [Full Text] [PDF]
|
|
|
|
 |
|
 N. M. El-Sayed, P. J. Myler, G. Blandin, M. Berriman, J. Crabtree, G. Aggarwal, E. Caler, H. Renauld, E. A. Worthey, C. Hertz-Fowler, et al. Comparative Genomics of Trypanosomatid Parasitic Protozoa Science, July 15, 2005; 309(5733): 404 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Ivens, C. S. Peacock, E. A. Worthey, L. Murphy, G. Aggarwal, M. Berriman, E. Sisk, M.-A. Rajandream, E. Adlem, R. Aert, et al. The Genome of the Kinetoplastid Parasite, Leishmania major Science, July 15, 2005; 309(5733): 436 - 442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Loke, X. Zang, L. Hsuan, R. Waitz, R. M. Locksley, J. E. Allen, and J. P. Allison Inducible costimulator is required for type 2 antibody isotype switching but not T helper cell type 2 responses in chronic nematode infection PNAS, July 12, 2005; 102(28): 9872 - 9877. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Donnelly, S. M. O'Neill, M. Sekiya, G. Mulcahy, and J. P. Dalton Thioredoxin Peroxidase Secreted by Fasciola hepatica Induces the Alternative Activation of Macrophages Infect. Immun., January 1, 2005; 73(1): 166 - 173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Nair, I. J. Gallagher, M. D. Taylor, P. Loke, P. S. Coulson, R. A. Wilson, R. M. Maizels, and J. E. Allen Chitinase and Fizz Family Members Are a Generalized Feature of Nematode Infection with Selective Upregulation of Ym1 and Fizz1 by Antigen-Presenting Cells Infect. Immun., January 1, 2005; 73(1): 385 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P. Beiting, S. K. Bliss, D. H. Schlafer, V. L. Roberts, and J. A. Appleton Interleukin-10 Limits Local and Body Cavity Inflammation during Infection with Muscle-Stage Trichinella spiralis Infect. Immun., June 1, 2004; 72(6): 3129 - 3137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Spencer, L. Shultz, and T. V. Rajan T Cells Are Required for Host Protection against Brugia malayi but Need Not Produce or Respond to Interleukin-4 Infect. Immun., June 1, 2003; 71(6): 3097 - 3106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rodriguez-Sosa, L. E. Rosas, J. R. David, R. Bojalil, A. R. Satoskar, and L. I. Terrazas Macrophage Migration Inhibitory Factor Plays a Critical Role in Mediating Protection against the Helminth Parasite Taenia crassiceps Infect. Immun., March 1, 2003; 71(3): 1247 - 1254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zang, P. Taylor, J. M. Wang, D. J. Meyer, A. L. Scott, M. D. Walkinshaw, and R. M. Maizels Homologues of Human Macrophage Migration Inhibitory Factor from a Parasitic Nematode. GENE CLONING, PROTEIN ACTIVITY, AND CRYSTAL STRUCTURE J. Biol. Chem., November 8, 2002; 277(46): 44261 - 44267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Noel, G. Hassanzadeh, G. Raes, B. Namangala, I. Daems, L. Brys, F. Brombacher, P. D. Baetselier, and A. Beschin Infection Stage-Dependent Modulation of Macrophage Activation in Trypanosoma congolense-Resistant and -Susceptible Mice Infect. Immun., November 1, 2002; 70(11): 6180 - 6187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Welch, L. Escoubet-Lozach, D. B. Sykes, K. Liddiard, D. R. Greaves, and C. K. Glass TH2 Cytokines and Allergic Challenge Induce Ym1 Expression in Macrophages by a STAT6-dependent Mechanism J. Biol. Chem., November 1, 2002; 277(45): 42821 - 42829. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Raes, P. De Baetselier, W. Noel, A. Beschin, F. Brombacher, and G. Hassanzadeh Gh. Differential expression of FIZZ1 and Ym1 in alternatively versus classically activated macrophages J. Leukoc. Biol., April 1, 2002; 71(4): 597 - 602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Harbord, M. Novelli, B. Canas, D. Power, C. Davis, J. Godovac-Zimmermann, J. Roes, and A. W. Segal Ym1 Is a Neutrophil Granule Protein That Crystallizes in p47phox-deficient Mice J. Biol. Chem., February 8, 2002; 277(7): 5468 - 5475. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
