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. 2004 May;20(5):623-35.
doi: 10.1016/s1074-7613(04)00107-4.

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

De'Broski R Herbert  1 , Christoph Hölscher, Markus Mohrs, Berenice Arendse, Anita Schwegmann, Magda Radwanska, Mosiuoa Leeto, Richard Kirsch, Pauline Hall, Horst Mossmann, Björn Claussen, Irmgard Förster, Frank Brombacher
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Free article

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

De'Broski R Herbert et al. Immunity. 2004 May.
Free article

Erratum in

  • Immunity. 2004 Sep;21(3):455

Abstract

Macrophage/neutrophil-specific IL-4 receptor alpha-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)IL-4Ralpha(-/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.

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