Alternatively activated macrophages induced by nematode infection inhibit proliferation via cell-to-cell contact.
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.
Loke
P
P
Institute of Cell, Animal and Population Biology, University of Edinburg, GB.
MacDonald
A S
AS
Robb
A
A
Maizels
R M
RM
Allen
J E
JE
D000818:Animals; D017178:Brugia malayi; D002450:Cell Communication; D002453:Cell Cycle; D002455:Cell Division; D002460:Cell Line; D005368:Filariasis / Q000276:immunology*; D015847:Interleukin-4 / Q000502:physiology; D008262:Macrophage Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018418:Th2 Cells / Q000502:physiology
D015847:Interleukin-4