Alternative macrophage activation is essential for survival during schistosomiasis and downmodulates T helper 1 responses and immunopathology

被引:594
作者
Herbert, DR [1 ]
Hölscher, C
Mohrs, M
Arendse, B
Schwegmann, A
Radwanska, M
Leeto, M
Kirsch, R
Hall, P
Mossmann, H
Clausen, BE
Förster, I
Brombacher, F
机构
[1] Univ Cape Town, Fac Hlth Sci, ZA-7925 Cape Town, South Africa
[2] Max Planck Inst Immunobiol, D-79108 Freiburg, Germany
[3] Univ Munich, Inst Med Microbiol Immunol & Hyg, D-81675 Munich, Germany
基金
英国医学研究理事会; 英国惠康基金; 新加坡国家研究基金会;
关键词
D O I
10.1016/S1074-7613(04)00107-4
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Macrophage/neutrophil-specific IL-4 receptor a-deficient mice (LysM(Cre)IL-4Ralpha(-/flox)) were generated to understand the role of IL-4/IL-13 responsive myeloid cells during Type 2 immune responses. LysM(Cre) IL4-Ralpha(-/flox) mice developed protective immunity against Nippostrongylus brasiliensis accompanied by T(H)2 development and goblet cell hyperplasia. In contrast, LysM(Cre)IL-4Ralpha(-/flox) mice were extremely susceptible to Schistosoma mansoni infection with 100% mortality during acute infection. Mortality was not dependent on neutrophils and occurred in the presence of T(H)2/Type 2 responses, granuloma formation, and egg-induced fibrosis. Death was associated with increased T(H)1 cytokines, hepatic and intestinal histopathology, increased NOS-2 activity, impaired egg expulsion, and sepsis. IL-10 was not able to compensate for the absence of IL-4/IL-13-activated alternative macrophages. Together, this shows that alternative macrophages are essential during schistosomiasis for protection against organ injury through downregulation of egg-induced inflammation.
引用
收藏
页码:623 / 635
页数:13
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