IL-18 regulates intestinal mastocytosis and Th2 cytokine production independently of IFN-gamma during Trichinella spiralis infection

Helmby, H; Grencis, RK; (2002) IL-18 regulates intestinal mastocytosis and Th2 cytokine production independently of IFN-gamma during Trichinella spiralis infection. Journal of immunology (Baltimore, Md, 169 (5). pp. 2553-60. ISSN 0022-1767 DOI:

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Expulsion of the gastrointestinal nematode Trichinella spiralis is associated with pronounced mastocytosis mediated by a Th2-type response involving IL-4, IL-10, and IL-13. Here we demonstrate that IL-18 is a key negative regulator of protective immune responses against T. spiralis in vivo. IL-18 knockout mice are highly resistant to T. spiralis infection, expel the worms rapidly and subsequently develop low levels of encysted muscle larvae. The increased speed of expulsion is correlated with high numbers of mucosal mast cells and an increase in IL-13 and IL-10 secretion. When normal mice were treated with rIL-18 in vivo, worm expulsion was notably delayed, and the development of mastocytosis and Th2 cytokine production was significantly reduced. The treatment had no effect on intestinal eosinophilia or goblet cell hyperplasia but specifically inhibited the development of mastocytosis. Addition of rIL-18 to in vitro cultures of bone marrow-derived mast cells resulted in a significant reduction in cell yields as well as in the number of IL-4-secreting mast cells. In vivo treatment of T. spiralis-infected IFN-gamma knockout mice with rIL-18 demonstrated that the inhibitory effect of IL-18 on mastocytosis and Th2 cytokine secretion is independent of IFN-gamma. Hence, IL-18 plays a significant biological role as a negative regulator of intestinal mast cell responses and may promote the survival of intestinal parasites in vivo.

Item Type: Article
Keywords: Animal, Cell Movement/genetics/immunology, Cells, Cultured, Comparative Study, Cytokines/antagonists & inhibitors/*biosynthesis/secretion, Immunity, Natural/genetics, Injections, Intraperitoneal, Interferon Type II/antagonists & inhibitors/*physiology/secretion, Interleukin-10/antagonists & inhibitors/genetics/secretion, Interleukin-13/antagonists & inhibitors/genetics/secretion, Interleukin-18/deficiency/genetics/*physiology, Interleukin-4/secretion, Interleukin-9/antagonists & inhibitors/genetics, Intestinal Diseases, Parasitic/genetics/*immunology/parasitology, Intestinal Mucosa/immunology/parasitology, Jejunal Diseases/genetics/immunology/parasitology, Lymph Nodes/immunology/pathology/secretion, Male, Mast Cells/immunology, Mastocytosis/genetics/*immunology/parasitology/prevention & control, Mesentery, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle, Skeletal/immunology/parasitology, RNA, Messenger/antagonists & inhibitors, Recombinant Proteins/administration & dosage, Support, Non-U.S. Gov't, Th1 Cells/immunology/secretion, Th2 Cells/*immunology/secretion, Trichinella spiralis/growth & development/*immunology, Trichinosis/genetics/*immunology/parasitology, Animal, Cell Movement, genetics, immunology, Cells, Cultured, Comparative Study, Cytokines, antagonists & inhibitors, biosynthesis, secretion, Immunity, Natural, genetics, Injections, Intraperitoneal, Interferon Type II, antagonists & inhibitors, physiology, secretion, Interleukin-10, antagonists & inhibitors, genetics, secretion, Interleukin-13, antagonists & inhibitors, genetics, secretion, Interleukin-18, deficiency, genetics, physiology, Interleukin-4, secretion, Interleukin-9, antagonists & inhibitors, genetics, Intestinal Diseases, Parasitic, genetics, immunology, parasitology, Intestinal Mucosa, immunology, parasitology, Jejunal Diseases, genetics, immunology, parasitology, Lymph Nodes, immunology, pathology, secretion, Male, Mast Cells, immunology, Mastocytosis, genetics, immunology, parasitology, prevention & control, Mesentery, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle, Skeletal, immunology, parasitology, RNA, Messenger, antagonists & inhibitors, Recombinant Proteins, administration & dosage, Support, Non-U.S. Gov't, Th1 Cells, immunology, secretion, Th2 Cells, immunology, secretion, Trichinella spiralis, growth & development, immunology, Trichinosis, genetics, immunology, parasitology
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Neglected Tropical Diseases Network
PubMed ID: 12193725
Web of Science ID: 177594100040


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