Alternative Macrophage Activation Is Essential for Survival during Schistosomiasis and Downmodulates T Helper 1 Responses and Immunopathology.
Herbert, De'Broski R 1,4; Holscher, Christoph 1,4,5; Mohrs, Markus 2,6; Arendse, Berenice 1; Schwegmann, Anita 1; Radwanska, Magda 1; Leeto, Mosiuoa 1; Kirsch, Richard 1; Hall, Pauline 1; Mossmann, Horst 2; Claussen, Bjorn 3,7; Forster, Irmgard 3; Brombacher, Frank *,1
[Article] Immunity. 20(5):623-635, May 2004.

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Summary: Macrophage/neutrophil-specific IL-4 receptor [alpha]-deficient mice (LysMCreIL-4R[alpha]-/flox) were generated to understand the role of IL-4/IL-13 responsive myeloid cells during Type 2 immune responses. LysMCreIL-4R[alpha]-/flox mice developed protective immunity against Nippostrongylus brasiliensis accompanied by TH2 development and goblet cell hyperplasia. In contrast, LysMCreIL-4R[alpha]-/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 TH2/Type 2 responses, granuloma formation, and egg-induced fibrosis. Death was associated with increased TH1 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.

(C) 2004Elsevier, Inc.