학술논문
Myeloid cell-specific expression of Ship1 regulates IL-12 production and immunity to helminth infection.
Document Type
Article
Author
Source
Subject
*HELMINTHIASIS
*CELL proliferation
*INOSITOL
*INTERLEUKINS
*WHIPWORMS
*LABORATORY mice
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Language
ISSN
1933-0219
Abstract
Helminth infection leads to the local proliferation and accumulation of macrophages in tissues. However, the function of macrophages during helminth infection remains unclear. SH2-containing inositol 5′-phosphatase 1 (Ship1, Inpp5d) is a lipid phosphatase that has been shown to play a critical role in macrophage function. Here, we identify a critical role for Ship1 in the negative regulation of interleukin (IL)-12/23p40 production by macrophages during infection with the intestinal helminth parasite Trichuris muris. Mice with myeloid cell-specific deletion of Ship1 (Ship1ΔLysM mice) develop a non-protective T-helper type 1 cell response and fail to expel parasites. Ship1-deficient macrophages produce heightened levels of IL-12/23p40 in vitro and in vivo and antibody blockade of IL-12/23p40 renders Ship1ΔLysM mice resistant to Trichuris infection. Our results identify a critical role for the negative regulation of IL-12/23p40 production by macrophages in the development of a protective TH2 cell response. [ABSTRACT FROM AUTHOR]