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. The infection is transmitted buy ingestion of cysts and the cyst wall contains large amounts of N-acetyl galactosamine (GalNAc) polymer. The macrophage galactose-binding lectin (MGL) is the dominant lectin capable of recognizing GalNAc. Our hypothesis is that recognition of cyst wall material by MGL plays a significant role in determining the outcome of infections by modulating both innate and adaptive immune responses. Sepcifically, we hypothesize that MGL2 on dendritic cells recongizes parasite glycans leading to release of cytokines that promote production of the cytokine IL-17 by both innate and adaptive lymphocytes. IL-17 has recently been shown to be essential for resolution of Giardia infections. The balance between these competing forces will determine whether infections are resolved rapidly or become chronic. We will address these hypotheses by examining infections in mice lacking cells which express MGL2 or which lack MGL2 itself. We wille examine immune rsponses in vivo and in vitro to both cysts and trophozoites to determine the ability of cyst wall carbohydrates to activate immune cells through MGL2. Finally, bone marrow chimeras will be used to identify specific roles of cytokine production by MGL2+ cells.

Public Health Relevance

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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Academic Research Enhancement Awards (AREA) (R15)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Pesce, John T
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Georgetown University
Schools of Arts and Sciences
United States
Zip Code
Coelho, Camila H; Singer, Steven M (2018) Recent advances in the Giardia-host relationship reveal danger lurking behind the smile. PLoS Negl Trop Dis 12:e0006625
Coelho, Camila Henriques; Durigan, Maurício; Leal, Diego Averaldo Guiguet et al. (2017) Giardiasis as a neglected disease in Brazil: Systematic review of 20 years of publications. PLoS Negl Trop Dis 11:e0006005
Barash, N R; Maloney, J G; Singer, S M et al. (2017) Giardia Alters Commensal Microbial Diversity throughout the Murine Gut. Infect Immun 85:
Fink, Marc Y; Singer, Steven M (2017) The Intersection of Immune Responses, Microbiota, and Pathogenesis in Giardiasis. Trends Parasitol 33:901-913
Bartelt, Luther A; Bolick, David T; Mayneris-Perxachs, Jordi et al. (2017) Cross-modulation of pathogen-specific pathways enhances malnutrition during enteric co-infection with Giardia lamblia and enteroaggregative Escherichia coli. PLoS Pathog 13:e1006471
Nooshadokht, Maryam; Kalantari-Khandani, Behjat; Sharifi, Iraj et al. (2017) Stool antigen immunodetection for diagnosis of Giardia duodenalis infection in human subjects with HIV and cancer. J Microbiol Methods 141:35-41
Li, Erqiu; Tako, Ernest A; Singer, Steven M (2016) Complement Activation by Giardia duodenalis Parasites through the Lectin Pathway Contributes to Mast Cell Responses and Parasite Control. Infect Immun 84:1092-1099
Coelho, Camila Henriques; Costa, Adriana Oliveira; Silva, Ana Carolina Carvalho et al. (2016) Genotyping and Descriptive Proteomics of a Potential Zoonotic Canine Strain of Giardia duodenalis, Infective to Mice. PLoS One 11:e0164946
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

Showing the most recent 10 out of 14 publications