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Myeloid cell-specific expression of Ship1 regulates IL-12 production and immunity to helminth infection

TitleMyeloid cell-specific expression of Ship1 regulates IL-12 production and immunity to helminth infection
Publication TypeJournal Article
Year of Publication2012
AuthorsHadidi, S, Antignano, F, Hughes, MR, Wang, SKH, Snyder, K, Sammis, GM, Kerr, WG, McNagny, KM, Zaph, C
JournalMUCOSAL IMMUNOLOGY
Volume5
Pagination535-543
Date PublishedSEP
ISSN1933-0219
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 (Ship1(Delta LysM) 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 Ship1(Delta LysM) 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 T(H)2 cell response.

DOI10.1038/mi.2012.29