IL-12 gene transfer alters gut physiology and host immunity in nematode-infected mice

Immune responses elicited by nematode parasite infections are characterized by T helper 2 (Th2) cell induction. The immunologic basis for changes in i ntestinal physiology accompanying nematode infection is poorly understood. This study examined whether worm expulsion and associated goblet cell hyper plasia and muscle contractility share a similar immune basis by shifting th e response from Th2 to Th1 using interleukin-12 (IL-12) overexpression. We used a single administration of recombinant adenovirus vector expressing IL -12 (Ad5IL-12) in Trichinella spiralis-infected mice. Ad5IL-12 administered 1 day after infection prolonged worm survival and inhibited infection-indu ced muscle hypercontractility and goblet cell hyperplasia. This was correla ted with upregulated interferon-gamma (IFN-gamma) expression and downregula ted IL-13 expression in the muscularis externa layer. We also observed incr eased IFN-gamma production and decreased IL-4 and IL-13 production from in vitro stimulated spleen and mesenteric lymph node cells of infected Ad5IL-1 2- treated mice. These results indicate that transfer and overexpression of the IL-12 gene during Th2-based nematode infection shifts the immune respo nse toward Th1 and delays worm expulsion. Moreover, the immune response shi ft abrogated the physiological responses to infection, attenuating both mus cle hypercontractility and goblet cell hyperplasia. These findings strongly indicate that worm expulsion, muscle hypercontractility, and goblet cell h yperplasia share a common immunologic basis and may be causally linked.