This Article Full Text Full Text (PDF) Other Versions of this Article: IAI.01042-07v1 76/4/1668    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hübner, M. P. Articles by Hoffmann, W. H. Search for Related Content PubMed PubMed Citation Articles by Hübner, M. P. Articles by Hoffmann, W. H.

 Previous Article  |  Next Article 

Infection and Immunity, April 2008, p. 1668-1677, Vol. 76, No. 4
0019-9567/08/$08.00+0     doi:10.1128/IAI.01042-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Microfilariae of the Filarial Nematode Litomosoides sigmodontis Exacerbate the Course of Lipopolysaccharide-Induced Sepsis in Mice

Marc P. Hübner,^1* Bastian Pasche,² Svetoslav Kalaydjiev,^3, Peter T. Soboslay,¹ Andreas Lengeling,² Hartwig Schulz-Key,¹ Edward Mitre,⁴ and Wolfgang H. Hoffmann¹

Institute of Tropical Medicine, University of Tübingen, 72074 Tübingen, Germany,¹ Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany,² Institute for Medical Microbiology, Immunology, and Hygiene, Technical University of Munich, 81675 Munich, Germany,³ Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814⁴

Received 27 July 2007/ Returned for modification 9 September 2007/ Accepted 28 January 2008

Helminths facilitate their own survival by actively modulating the immune systems of their hosts. We investigated the impacts that different life cycle stages of the rodent filaria Litomosoides sigmodontis have on the inflammatory responses of mice injected with sublethal doses of lipopolysaccharide (LPS). Mice infected with female adult worms from prepatent infections, worms which have not yet started to release microfilariae, developed lower levels of proinflammatory cytokines in the peripheral blood after LPS challenge than sham-treated controls, demonstrating that female adult worms can mitigate the innate immune response. The presence of microfilariae in mice, however, through either direct injection or implantation of microfilaria-releasing adult female worms, turned the LPS challenge fatal. This lethal outcome was characterized by increased plasma levels of gamma interferon (IFN-), tumor necrosis factor alpha (TNF-), interleukin 12 (IL-12), and IL-6, greater numbers of macrophages and granulocytes in the peripheral blood, and decreased body temperatures in microfilaria-infected mice. Microfilaria-infected mice deficient in IFN- receptor and TNF receptor 1 had increased survival rates after LPS challenge compared to immune-competent mice, suggesting that microfilariae worsen LPS-induced sepsis through actions of IFN- and TNF-. In summary, we have demonstrated that infection of mice with L. sigmodontis female adult worms from prepatent infections protects mice injected with LPS whereas microfilariae worsen LPS-induced sepsis through the induction of proinflammatory cytokines and upregulation of granulocytes, NK cells, and monocytes in the peripheral blood.

Published ahead of print on 4 February 2008.

Editor: J. F. Urban, Jr.

Present address: Faculty of Life Sciences, The University of Manchester, Manchester M13 9PT, United Kingdom.