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NK cell binding protein (NKBP) - chronic hookworm infections in humans are marked by high levels of IL-10 and depressed levels of IL-4, a surprising finding given the elevated levels of IL-4 in other helminth infections. We have identified secreted proteins of the human hookworm, Necator americanus, which bind specifically to Natural Killer cells and no other cell type. Moreover, these proteins induce NK cells to secrete high levels of IFN- , an intriguing finding given the absence of a pronounced Th2 response (usually associated with immune clearance of helminths) in human hookworm infections. Future work in this area will explore the effects of hookworm secretory products on the inability of humans to mount protective immune responses to this pathogen. We will also purify the NK cell-binding protein, identify its NK cell receptor, and explore its potential as a pro-inflammatory adjuvant and specific marker for NK cells.