Gastrointestinal (GI) nematode infections are an important public health and economic concern. Experimental studies have shown that resistance to infection requires CD4 ؉ T helper type 2 (Th2) cytokine responses characterized by the production of IL-4 and IL-13. However, despite >30 years of research, it is unclear how the immune system mediates the expulsion of worms from the GI tract. Here, we demonstrate that a recently described intestinal goblet cell-specific protein, RELM␤͞FIZZ2, is induced after exposure to three phylogenetically distinct GI nematode pathogens. Maximal expression of RELM␤ was coincident with the production of Th2 cytokines and host protective immunity, whereas production of the Th1 cytokine, IFN-␥, inhibited RELM␤ expression and led to chronic infection. Furthermore, whereas induction of RELM␤ was equivalent in nematode-infected wild-type and IL-4-deficient mice, IL-4 receptor-deficient mice showed minimal RELM␤ induction and developed persistent infections, demonstrating a direct role for IL-13 in optimal expression of RELM␤. Finally, we show that RELM␤ binds to components of the nematode chemosensory apparatus and inhibits chemotaxic function of a parasitic nematode in vitro. Together, these results suggest that intestinal goblet cell-derived RELM␤ may be a novel Th2 cytokine-induced immune-effector molecule in resistance to GI nematode infection.

Host-seeking behavior by parasitic nematodes relies heavily on chemical cues emanating from potential hosts. Nonspecific cues for Strongyloides stercoralis, a nematode that infects humans and a few other mammals, include carbon dioxide and sodium chloride; however, the characteristic species specificity of this parasite suggested the existence of other, more specific cues. Here we show that the infective larva of S. stercoralis is strongly attracted to an extract of mammalian skin and that the active component in this skin extract is urocanic acid. Urocanic acid, a histidine metabolite, is particularly abundant in mammalian skin and skin secretions, suggesting that it serves as an attractant specific to mammalian hosts. The attractant activity of urocanic acid is suppressed by divalent metal ions, suggesting a possible strategy for preventing infection.histidine ͉ host-seeking ͉ chemotaxis ͉ topical preventative

The parasitic nematode Strongyloides stercoralis, has several alternative developmental pathways. Upon exiting the host (humans, other primates and dogs) in faeces, 1st-stage larvae (L1) can enter the direct pathway, in which they moult twice to reach the infective 3rd-stage. Alternatively, if they enter the indirect pathway, they moult 4 times and become free-living adults. The choice of route depends, in part, on environmental cues. In this investigation it was shown that at temperatures below 34 degrees C the larvae enter the indirect pathway and develop to free-living adulthood. Conversely, at temperatures approaching body temperature (34 degrees C and above), that are unfavorable for the survival of free-living stages, larvae develop directly to infectivity. The time-period within the L1's development during which temperature influenced the choice of the pathway depended on the temperature, but, at any given temperature, occurred approximately in the middle of the time-span spent in the L1 stage, which varied inversely with temperature. This critical period was associated with the time-interval in which the number of cells in the genital primordium began to increase, thus providing a morphological marker for the pathway decision in individual worms. Sensing the environment is the function of the amphidial neurons, and therefore we examined the role of individual amphidial neurons in controlling entry into the direct pathway to infectivity. The temperature-sensitive developmental switch is controlled by the neuron pair ALD (which also controls thermotaxis), as seen by the loss of control when these neurons are ablated. Thus, in S. stercoralis a single amphidial neuron pair controls both developmental and behavioural functions.