|VAN ROOIJEN, NICO|
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 9/1/2005
Publication Date: 11/15/2005
Citation: Anthony, R., Urban Jr, J.F., Alem, F., Hamed, H., Van Rooijen, N., Gause, W. 2005. Alternatively activated macrophages accumulate at the host parasite interface and contribute to protection against a nematode parasite.. Meeting Abstract.
Technical Abstract: The mechanisms leading to host protection against intestinal nematode parasites are little understood, although physiological changes in the intestines are sighted as primary host-defense mechanisms. The memory response to Heligmosomoides polygyrus, a natural murine gastrointestinal helminth parasite, is associated with rapid accumulation of CD4+ T cells adjacent to parasitic larvae in the sub mucosa of the small intestine, and results in expulsion of adult worms by day 14 post infection. Laser-capture micro dissection was used in combination with fluorescence immunohistochemstry to isolate CD4+, Gr1+, and CD4- Gr1- cells infiltrating the tissue adjacent to parasitic larvae and to measure cytokine gene expression; high elevations in IL-4 and IL-13 mRNA but no IFN-gamma were detected in CD4+ and Gr1+ populations. Further histological analysis demonstrated that macrophages, accumulating around the parasite, express the IL-4 receptor and develop an alternatively activated phenotype in a stat6 dependant manner. Depletion of these cells during a challenge infection by administration of clodronate liposomes abrogated the protective memory response and blocked adult worm expulsion; however, the egg production by these adults was greatly reduced. Our findings demonstrate that these alternatively activated macrophages play an important role in intestinal function leading to parasite clearance.