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Originally published online as doi:10.1189/jlb.1007689 on November 20, 2007

Published online before print November 20, 2007
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(Journal of Leukocyte Biology. 2008;83:314-324.)
© 2008 by Society for Leukocyte Biology

A systemic granulomatous response to Schistosoma mansoni eggs alters responsiveness of bone marrow-derived macrophages to Toll-like receptor agonists

Amrita D. Joshi, Tracy Raymond, Ana L. Coelho, Steven L. Kunkel and Cory M. Hogaboam1

Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA

1 Correspondence: Department of Pathology, University of Michigan Medical School, 4057 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-0602, USA. E-mail: hogaboam{at}med.umich.edu

ABSTRACT

Macrophages play a pivotal role in innate and acquired immune responses to Schistosoma mansoni. Classical (M1) or alternative (M2) activation states of these cells further delineate their roles in tissue damage through innate immunity or fibrotic remodeling, respectively. In the present study, we addressed the following question: Does systemic Th2-type cytokine polarization evoked by S. mansoni affect macrophage differentiation and activation? To this end, we analyzed bone marrow-derived macrophages from mice with S. mansoni egg-induced pulmonary granulomas and unchallenged (or naïve) mice to determine their activation state and their response to specific TLR agonists, including S. mansoni egg antigens. Unlike naïve macrophages, macrophages from Th2-polarized mice constitutively expressed significantly higher "found in inflammatory zone-1" (FIZZ1) and ST2 (M2 markers) and significantly lower NO synthase 2, CCL3, MIP-2, TNF-{alpha}, and IL-12 (M1 markers). Also, compared with naïve macrophages, Th2-polarized macrophages exhibited enhanced responses to the presence of specific TLR agonists, which consistently induced significantly higher levels of gene and protein levels for M2 and M1 markers in these cells. Together, these data show that signals received by bone marrow precursors during S. mansoni egg-induced granuloma responses dynamically alter the development of macrophages and enhance the TLR responsiveness of these cells, which may ultimately have a significant effect on the pulmonary granulomatous response.

Key Words: alternative activation • classical activation • soluble egg antigen




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