Submitted to: Journal of Immunology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 1/10/2000
Publication Date: 4/15/2000
Citation: Urban Jr, J.F., Schopf, L.R., Morris, S., Orekhova, T., Madden, K.B., Betts, C.J., Gamble, H.R., Byrd, C., Donaldson, D., Else, K. 2000. Stat6 signaling promotes protective immunity against trichinella spiralis thr0ugh a mast cell- and t cell-dependent mechanism. Journal of Immunology. 164:2046-2052 (2000) Interpretive Summary: Gastrointestinal (GI) nematode parasites represent an economic and herd health problem for producers of livestock. Immunity against parasites has been difficult to establish, but is an essential alternative control strategy to the use of drugs that can affect food quality. A basic understanding of the immune response to GI nematode parasites is critical to the production and design of novel vaccination strategies. The current report shows that an intracellular Stat6 molecule can regulate protection against two different GI nematode parasites, however, the protective mechanisms are essentially different. This suggests that the host response to infection is a general enough to expel parasites that are very different in their location and interaction with the host intestine. This information will provide government, academic and industrial scientists with a central molecule that is key to an immune response cascade that could affect a variety of parasites infections of economic importance and that compromise food safety. Improvements in vaccination procedures would make immunity to GI parasites more practical.
Technical Abstract: Studies in mice infected with the gastrointestinal (GI) nematode parasite, Nippostrongylus brasiliensis, show that activation of Stat6 by IL-4/IL-13 is essential for parasite expulsion, but is not required for IL-4/IL-13 production and negatively regulates intestinal mastocytosis. It was postulated that protection against Trichinella spiralis would be Stat6-independent because expulsion is mast cell-dependent. However, Stat activation by IL-4/IL-13 is required for expulsion of T. spiralis as well as for development of type 2 cytokine responses and intestinal mastocytosis. Both mast cells and T cells are required for IL-4-dependent expulsion of T. spiralis, but not N. brasiliensis. Thus, Stat6 signaling is required for host protection against both GI parasites, but through different mechanisms. The induction of multiple effector mechanisms by Stat6 signaling provides a way for a patterned-cytokine response to be protective against a variety of GI nematode parasites that inhabit different regions of the intestine.