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

S Hadidi, F Antignano, MR Hughes, SKH Wang, K Snyder, GM Sammis, WG Kerr, KM McNagny, C Zaph

Research output: Contribution to journalArticleResearchpeer-review

11 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)535-543
Number of pages9
JournalMucosal Immunology
Volume5
Issue number5
DOIs
Publication statusPublished - Sep 2012
Externally publishedYes

Cite this