TY - JOUR
T1 - Lack of eosinophil peroxidase or major basic protein impairs defense against murine filarial infection
AU - Specht, Sabine
AU - Saeftel, Michael
AU - Arndt, Manuela
AU - Endl, Elmar
AU - Dubben, Bettina
AU - Lee, Nancy A.
AU - Lee, James J.
AU - Hoerauf, Achim
PY - 2006/9
Y1 - 2006/9
N2 - Eosinophils are a hallmark of allergic diseases and helminth infection, yet direct evidence for killing o66 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.
AB - Eosinophils are a hallmark of allergic diseases and helminth infection, yet direct evidence for killing o66 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.
UR - http://www.scopus.com/inward/record.url?scp=33748074819&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748074819&partnerID=8YFLogxK
U2 - 10.1128/IAI.00329-06
DO - 10.1128/IAI.00329-06
M3 - Article
C2 - 16926417
AN - SCOPUS:33748074819
SN - 0019-9567
VL - 74
SP - 5236
EP - 5243
JO - Infection and Immunity
JF - Infection and Immunity
IS - 9
ER -