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

• Published in: Mucosal immunology Vol. 5; no. 5; pp. 535 - 543
• Main Authors: Hadidi, S, Antignano, F, Hughes, M R, Wang, S K H, Snyder, K, Sammis, G M, Kerr, W G, McNagny, K M, Zaph, C
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.09.2012
• Subjects: Animals; Cells, Cultured; Gene Expression Regulation - genetics; Immunity; Inositol Polyphosphate 5-Phosphatases; Interleukin-12 - genetics; Interleukin-12 - metabolism; Intestinal Diseases, Parasitic - immunology; Macrophages - immunology; Mice; Mice, Mutant Strains; Myeloid Cells - metabolism; Organ Specificity; Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; Phosphoric Monoester Hydrolases - genetics; Phosphoric Monoester Hydrolases - metabolism; Sequence Deletion - genetics; Th1 Cells - immunology; Th2 Cells - immunology; Trichuriasis - immunology; Trichuris - immunology
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/mi.2012.29

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(ΔLysM) 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(ΔLysM) 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.