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

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.

journal_name

Immunity

journal_title

Immunity

authors

Herbert DR,Hölscher C,Mohrs M,Arendse B,Schwegmann A,Radwanska M,Leeto M,Kirsch R,Hall P,Mossmann H,Claussen B,Förster I,Brombacher F

doi

10.1016/s1074-7613(04)00107-4

keywords:

subject

Has Abstract

pub_date

2004-05-01 00:00:00

pages

623-35

issue

5

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(04)00107-4

journal_volume

20

pub_type

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