Alternatively activated macrophages induced by nematode infection inhibit proliferation via cell-to-cell contact

Eur J Immunol. 2000 Sep;30(9):2669-78. doi: 10.1002/1521-4141(200009)30:9<2669::AID-IMMU2669>3.0.CO;2-1.


The cytokine microenvironment is thought to play an important role in the generation of immunoregulatory cells. Nematode infections are commonly associated with Th2 cytokines and hyporesponsive T cells. Here we show that IL-4-dependent macrophages recruited in vivo by the nematode parasite Brugia malayi actively suppress the proliferation of lymphocytes on co-culture in vitro. These alternatively activated macrophages block proliferation by cell-to-cell contact, implicating a receptor-mediated mechanism. Further, the proliferative block is reversible and is not a result of apoptosis. Suppressed cells accumulate in the G1 and G2/M phase of the cell cycle. Interestingly, the G1 and G2/M block correlates with increased levels of Ki-67 protein, suggesting a mechanism that affects degradation of cell cycle proteins. We also show that, in addition to lymphocyte cell lines of murine origin, these suppressive cells can inhibit proliferation of a wide range of transformed human carcinoma lines. Our data reveal a novel mechanism of proliferative suppression induced by a parasitic nematode that acts via IL-4-dependent macrophages. These macrophages may function as important immune regulatory cells in both infectious and noninfectious disease contexts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brugia malayi
  • Cell Communication*
  • Cell Cycle
  • Cell Division
  • Cell Line
  • Filariasis / immunology*
  • Interleukin-4 / physiology
  • Macrophage Activation*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Th2 Cells / physiology


  • Interleukin-4