Giardia lamblia is a common cause of both acute and chronic diarrheal disease in humans worldwide. It has been shown that mast cells, IL-6 and TNF-alpha are substantially involved in the early control of G. lamblia infection in mice. However, no studies have yet been reported concerning the interaction between mast cell and Giardia, as well as the mast cells mediators generated in response to Giardia infection. In this study we demonstrated the direct activation of mast cells by G. lamblia live trophozoites or trophozoite-derived antigens followed by an increase in tryptase expression and a significant release of the preformed mediator histamine. In addition, parasite derived antigens increased TNF-alpha and de novo synthesized cytokine IL-6, at the mRNA and protein level. These results strongly suggest that mast cells might be an important source not only of IL-6 but also of TNF-alpha during Giardia infection, playing an important role in the outcome of the infection. (c) 2010 Elsevier Inc. All rights reserved.