Giardia lamblia is the most common protozoan cause of diarrhea in the world. It infects ~500 million people worldwide, often resulting in nutrient malabsorption which can lead to physical and cognitive developmental defects in children. Recent data suggest that the parasite is able to glycosylate secreted and surface proteins with N-acetylglucosamine and that recognition of this sugar by the mannose binding lectin (MBL) can activate the complement cascade. Our hypothesis is that recognition of parasite glycoproteins by host lectins plays a significant role in activating both innate and adaptive immune responses. We will address this specifically by examining infections in mice lacking host lectins and examining the impact on the course of infection and the innate and adaptive immune responses.
Giardia is the most commonly diagnosed protozoan cause of diarrhea in the United States. This proposal seeks to understand how the body's immune system initially recognizes the infecting parasite and determines whether and what kind of immune response to produce. This information is essential for developing vaccines against Giardia, as well as understanding how dysregulation of intestinal immunity leads to syndromes such as celiac, disease, food allergies and Crohn's disease.
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|Tosh, Kevin W; Mittereder, Lara; Bonne-Annee, Sandra et al. (2016) The IL-12 Response of Primary Human Dendritic Cells and Monocytes to Toxoplasma gondii Is Stimulated by Phagocytosis of Live Parasites Rather Than Host Cell Invasion. J Immunol 196:345-56|
|Keselman, Aleksander; Li, Erqiu; Maloney, Jenny et al. (2016) The Microbiota Contributes to CD8+ T Cell Activation and Nutrient Malabsorption following Intestinal Infection with Giardia duodenalis. Infect Immun 84:2853-60|
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