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Infection and Immunity, September 2006, p. 5236-5243, Vol. 74, No. 9
0019-9567/06/$08.00+0 doi:10.1128/IAI.00329-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Michael Saeftel,1,
Manuela Arndt,2
Elmar Endl,3
Bettina Dubben,1
Nancy A. Lee,4
James J. Lee,4 and
Achim Hoerauf1*
Institute for Medical Microbiology, Immunology and Parasitology, Friedrich-Wilhelm University Bonn, 53105 Bonn, Germany,1 Department of Helminthology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany,2 Institute for Molecular Medicine and Experimental Immunology, Friedrich-Wilhelm University Bonn, 53105 Bonn, Germany,3 Department of Biochemistry and Molecular Biology, Mayo Clinic Scottsdale, Scottsdale, Arizona 852594
Received 28 February 2006/ Returned for modification 17 April 2006/ Accepted 19 June 2006
Eosinophils are a hallmark of allergic diseases and helminth infection, yet direct evidence for killing of helminth parasites by their toxic granule products exists only in vitro. We investigated the in vivo roles of the eosinophil granule proteins eosinophil peroxidase (EPO) and major basic protein 1 (MBP) during infection with the rodent filaria Litomosoides sigmodontis. Mice deficient for either EPO or MBP on the 129/SvJ background developed significantly higher worm burdens than wild-type mice. Furthermore, the data indicate that EPO or MBP is involved in modulating the immune response leading to altered cytokine production during infection. Thus, in the absence of MBP, mice showed increased interleukin-10 (IL-10) production after stimulation of macrophages from the thoracic cavity where the worms reside. In addition to elevated IL-10 levels, EPO/ mice displayed strongly increased amounts of the Th2 cytokine IL-5 by CD4 T cells as well as a significantly higher eosinophilia. Interestingly, a reduced ability to produce IL-4 in the knockout strains could even be seen in noninfected mice, arguing for different innate propensities to react with a Th2 response in the absence of either EPO or MBP. In conclusion, both of the eosinophil granule products MBP and EPO are part of the defense mechanism against filarial parasites. These data suggest a hitherto unknown interaction between eosinophil granule proteins, defense against filarial nematodes, and cytokine responses of macrophages and CD4 T cells.
S.S. and M.S. contributed equally to this study.
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